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This study is aimed at identifying risk factors of Low Anterior Resection Syndrome following ileostomy reversal in rectal cancer patients who had undergone preventive ileostomy. This retrospective analysis was conducted on a cohort of 605 patients treated at the Fourth Hospital of Hebei Medical University between January 2018 and December 2021. These patients were grouped based on LARS score, and Clinical and follow-up data were collected to conduct univariate analyses of potential factors influencing LARS occurrence based on variable type. Variables with statistical significance were included in a logistic regression model to analyze potential influences on the occurrence of LARS. Univariate and Multivariate logistic regression analysis showed that N2 stage (OR = 2.290 95%CI: 1.076-4.873, P = 0.031), chemoradiotherapy (OR = 2.271, 95%CI: 1.246-4.138, P = 0.007), and anastomosis height (OR = 0.836, 95%CI: 0.717-0.975, P = 0.022) were independent influences on the occurrence of LARS. In model 3 (adjusting for all covariates), the relationship between anastomotic height and patient LARS status showed a negative correlation. In subgroup analyses, there were significant differences in the effect of anastomotic height on LARS in subgroups with different hemoglobin concentrations. A high occurrence rate of LARS is observed in rectal cancer patients with preventive ileostomy reversal. N2 stage, history of chemoradiotherapy, and anastomotic height are independent influence factors for the occurrence of major LARS after ileostomy reversal., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study received approval from the Ethics Committee of the Fourth Hospital of Hebei Medical University (approval number 2021111), and all patients provided informed consent before their inclusion in the study, adhering to ethical guidelines and standards., (© 2024. The Author(s).)

Purpose: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC)., Methods and Materials: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects., Results: In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P < .001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P < .001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P = .003; median PFS, 14.2 vs 10.6 months; P = .002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P < .001) and esophagitis (11.2% vs 2.4%, P = .006)., Conclusions: The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent radiotherapy combined with weekly chemotherapy in patients with cervical cancer., Methods: From September 2019 to November 2020, 180 patients with cervical cancer who required concurrent chemoradiotherapy (CCRT) were enrolled in this study. The patients were randomly divided into the following three groups at a ratio of 1:1:1: Group A (PEG-rhG-CSF), Group B (PEG-rhG-CSF + rhG-CSF) and the control group (rhG-CSF). Cisplatin or carboplatin was administered weekly. The primary endpoint was the incidence of grade 3/4 neutropenia. The secondary endpoints were the incidence of febrile neutropenia (FN), delay of radiotherapy, chemotherapy dose reduction, rate of PFS at 2 years and 3 years, and incidence of adverse reactions., Results: Sixty patients were randomly assigned to each group. Two patients in Group B withdrew from the trial for personal reasons. The incidence of grade 1/2 neutropenia in the Control group was significantly lower than that in Group A and Group B (P < 0.001). However, the incidence of grade 3/4 neutropenia in the Control group was significantly greater than that in Group A and Group B (P < 0.001). There was no significant difference in the incidence of FN among the three groups (P = 0.771). The rate of platinum dose reduction in Group A (6.7%) and Group B (5.2%) was significantly lower than that in the Control group (30.0%) (P < 0.001). The delay rate of radiotherapy in Group A (10%) and Group B (13.8%) was obviously inferior to that in the Control group (31.7%) (P = 0.006). The 2-year PFS rates of Group A, Group B, and the Control group were 93.3%, 98.3%, and 91.7%, respectively, with no statistically significant difference (P = 0.270). The 3-year PFS rates were 89.8%, 94.1%, and 84.9%, respectively, with no statistically significant difference (P = 0.178). No treatment-related serious adverse events occurred in any of the patients., Conclusion: In Group A and Group B, The prophylactic application of PEG-rhG-CSF during conventional chemoradiotherapy combined with weekly chemotherapy for patients with cervical cancer can reduce the incidence of grade 3/4 neutropenia and does not increase the incidence of adverse reactions when compared to Control group., Trial Registration: chictr.org.cn, ChiCTR1900026309, registered 29 September 2019-prospectively registered., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University (No. 2019221). All patients signed informed consent forms. Consent for publication The study received written informed consent for publication by all patients. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis., Methods: A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records., Results: Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm 2 (range 9-2025 mm 2 ), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm 2 (range 0-1600 mm 2 ). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7-60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009)., Conclusion: The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment., Methods: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm 2 /m 2 ) and volumetric sarcopenia (volumetric SMI <180.4 cm 3 /m 3 ). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored., Results: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045)., Conclusions: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions., Competing Interests: Declaration of competing interest Soon Ho Yoon has stocks and stock options of MEDICAL IP. Other authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer., Methods: This is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction., Results: Approximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present., Conclusions: Lower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT., Competing Interests: Declaration of competing interest Gabriela Villaca Chaves reports financial support, administrative support, equipment, drugs, or supplies, and travel were provided by FAPERJ. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sexual health is an important survivorship issue in cervical cancer. We assessed patient-reported sexual health outcomes and correlations with oncologist-assessed vaginal toxicity (VT)., Methods: This was a prospective, cross-sectional study of stage IB-IVA cervical cancer patients treated with definitive chemoradiation, who completed a socio-demographic questionnaire and the following patient-reported-outcomes (PROs): Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS). VT was assessed using the CTCAE v4.0. Sociodemographic, clinical data, PROs and VT were summarized using descriptive statistics; correlations were evaluated using linear regression analyses., Results: Between August 2018 and April 2022, 73 patients were analyzed. Median age was 49 (range 25-81), 57.5% had vaginal involvement at diagnosis and 76.9% were partnered. Sexual dysfunction (FSFI score ≤ 26), sexual distress (FSDS-R ≥ 11), severe menopausal symptoms (MRS ≥ 17), anxiety (HAD-Anxiety >7) and depression (HAS-Depression >7) were reported in 86.3%, 54.5%, 36.2%, 46.6% and 24.7%, respectively. Grade 2+ VT was reported in 27.4%. No significant associations were found between PROs and VT. On multivariable analysis, non-partnered status, use of hormone replacement therapy, and International Commission on Radiation Units and Measurements - rectovaginal dose (ICRU-RV) >65Gy were associated with worse sexual health (p < 0.005)., Conclusion: Cervical cancer patients self-report high rates of sexual distress, dysfunction and menopause symptoms. Discordance between oncologist-assessed VT and PROs highlights the importance of evaluating the patient's experience. Proactive treatment of menopausal symptoms and attention to radiotherapy doses to the vagina should be considered., Competing Interests: Declaration of competing interest Dr. Kathy Han was on the Astra Zeneca Cervical Cancer Radiation Oncology and Merck Gynaecological Cancer Advisory Board. All the other co-authors report no conflict of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: It is unclear how the duration and tapering pattern of corticosteroid therapy for pneumonitis changed after the introduction of durvalumab consolidation therapy., Methods: We retrospectively evaluated the medical records of patients diagnosed with nonsmall cell lung cancer who received chemoradiotherapy between January 2014 and December 2020., Results: Data for 135 patients treated before durvalumab approval and 100 patients treated with durvalumab after its approval were analyzed. In both groups, more than 70% were male, with a median age of 66 y. Approximately 85% were smokers, and the most common tumor histology was adenocarcinoma. Most patients were treated with doses of 60 and 66 Gy (n = 127 [94%] vs. n = 95 [95%]). Among the patients treated with durvalumab, 57%, 38%, and 5% had grade 1, grade 2, and grade 3 pneumonitis; none had grade 4 or 5 pneumonitis. Patients treated with durvalumab exhibited a longer duration of corticosteroid therapy for pneumonitis (17 wk; range: 2-88 wk) than patients not treated with durvalumab (7 wk; range: 0.4-21 wk; P < 0.001). Pneumonitis relapse was more frequent in patients treated with durvalumab (n = 8; 23%) than in patients not treated with durvalumab (n = 2; 7%). Among the 8 patients treated with durvalumab, 2 had recurrent pneumonitis, 1 could not terminate corticosteroids., Conclusions: Our data show that durvalumab prolongs the duration of corticosteroid therapy and increases the complexity of corticosteroid tapering patterns. This study can help manage pneumonitis caused by immune checkpoint inhibitors and other drugs used after chemoradiotherapy in routine practice and clinical trials., Competing Interests: Disclosure Dr. Horinouchi has received personal fees from AstraZeneca, MSD, Eli Lilly, Ono, BMS, Chugai, Roche, Amgen, Abbvie and grants from MSD, Abbvie, AstraZeneca, BMS, Ono, Daiichi-Sankyo, Janssen, Chugai, Roche. Dr.Shinno has received personal fees from AstraZeneca, BMS, Chugai, Ono, Eli Lilly and grants from Ono, Janssen, Japan Clinical Research Operations, Taiho, Bayer Gilead. Dr.Okuma has received personal fees from AstraZeneca, Boehringer Ingerheim, Chugai, Ely-Lilly, Esai, Takeda, MSD and grants from AstraZeneca, MSD. Dr.Yoshida has received personal fees from Novartis, Daiichi-Sankyo, AstraZeneca, MSD, Chugai, BMS, Ono, Takeda, Pfizer, Lilly, Merck and grants from Novartis, Abbvie, Amgen, Daiichi-Sankyo, AstraZeneca, MSD, Chugai, Astellas, Medpace, Boehringer Ingelheim, BMS, Ono, Merck. Dr.Goto has received personal fees from Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis. Merck, Thermo Fischer and grants from AstraZeneca, Pfizer, Abbvie, Eli Lilly, Pfizer, Bristol Myers Squibb, Ono, Novartis, Kyorin, DaiichiSankyo, Novartis. Dr.Yamamoto has received personal fees from Ono, Chugai, Daiichi-Sankyo, Eisai, Takeda, Boehringer Ingelheim, Cmic, Merck, Healiosand and grants from Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, Abbvie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, Ono, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic, Inventis Bio, Rakuten Medical. Dr.Kusumoto has received personal fees from Daiichi Sankyo, AstraZeneka and grants from Canon Medical Systems. Dr.Ohe has received personal fees from AstraZeneca, Chugai, Eli Lilly, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, Eisai Daiichi-Sankyo and grants from AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO. The remaining Authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Chemoradiotherapy (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC) has undergone advances, including increased overall survival (OS) when combined with immune checkpoint blockade (ICB), and using cardiac-sparing techniques to reduce the radiotoxicity. This research investigated 1) how radiotherapy schedules can be optimised with CRT-ICB schemes, and 2) how cardiac-sparing might change the OS for concurrent CRT (cCRT)., Methods and Materials: Survival data and dosimetric indices were sourced from published studies, with 2-year OS standardised and the hazard ratio of mean heart dose (MHD) against radiotoxicity tabulated in purpose. A published CRT dose-response model was selected, then modified with ICB and cardiac-sparing hypotheses. Models were maximum likelihood fitted, then visualised the prediction outcomes after bootstrapping., Results: The modelled 2-year OS rate of cCRT-ICB reached 71 % (95 % confidence intervals, CI 62 %, 84 %) and 66 % (95 % CI: 53 %, 81 %) for stage IIIA and IIIB/C, respectively, given 60 Gy in 2 Gy-per-fraction. 60 Gy in 30 fractions remained the best schedule for cCRT-ICB, whereas modest dose de-escalation to 55 Gy only reduced the OS in 2 %. Sequential CRT (sCRT)-ICB provided 6 % OS increases versus the best OS rate achieved by sCRT alone. Photon MHD-sparing achieved a 5-10 % increase in modelled 2-year OS, with protons providing a further roughly 5-10 % increase., Conclusion: Neither dose-escalation nor de-escalation relative to 60 Gy in 30 fractions influenced the survival with cCRT-ICB, while 5 Gy dose de-escalation might benefit patients with heavily irradiated organs at risk. Cardiac-sparing improved OS, and protons provided advantages for tumours anatomically overlapped or lay below the heart., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT., Methods and Materials: Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients., Results: The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women., Conclusions: HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The effectiveness and safety of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in elderly patients with locoregionally advanced nasopharyngeal carcinomas (LANPCs) remain subjects of debate. This study evaluated the efficacy of IC+CCRT compared to CCRT alone in elderly LANPC patients., Materials and Methods: This retrospective, single-center study analyzed 335 elderly patients diagnosed with stage III or IVa NPC who received CCRT with or without IC between 2010 and 2016. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival rates. Multivariate analysis using Cox proportional hazards regression model was conducted to assess prognostic risk factors. Toxicities were compared using the χ 2 test., Results: The median follow-up duration was 69.3 months (interquartile range: 42.7-72.6). Baseline clinical characteristics were well-balanced between groups. No significant differences were observed between IC+CCRT and CCRT for any survival-related endpoints, including overall survival (hazard ratio [HR] = 1.26, 95 % confidence interval [CI]: 0.89-1.77, p = 0.188), locoregional relapse-free survival (HR=1.03, 95 % CI: 0.56-1.91, p = 0.913), distant metastasis-free survival (HR=1.39, 95 % CI: 0.90-2.16, p = 0.139), and failure-free survival (HR = 1.25, 95 % CI: 0.85-1.83, p = 0.255). However, the incidence and severity of acute and late toxicities were significantly higher in the IC+CCRT group compared to the CCRT group., Conclusion: In elderly LANPC patients, the addition of IC to CCRT did not improve survival outcomes, but was associated with significant toxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor before the start of CRT to improve PTC., Methods and Materials: Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1 year, and the hypothesis was that the 1-year PTC rate would be ≥90%. Secondary objectives included objective response rate, regional and distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional magnetic resonance imaging and blood-based miRNA analysis., Results: The study enrolled 21 patients (10 men and 11 women); the median age was 62 years (range, 52-78). The median pretreatment primary tumor size was 5.0 cm (range, 1.0-8.3). The most common nonhematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 nonhematologic toxicity occurred (respiratory failure/radiation pneumonitis), and no grade 5 toxicities occurred. The objective response rate at 3 and 6 months was 72.7% and 80.0%, respectively, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control rates were 81.6% and 70.3%, respectively. Disease-free survival and overall survival at 2 years were 46.1% and 50.3%, respectively, and median survival was 37.8 months. Functional magnetic resonance imaging detected a mean relative decrease in blood oxygenation level-dependent signal of -87.1% (P = .05), and miR.142.3p was correlated with increased risk of grade ≥3 pulmonary toxicity (P = .01)., Conclusions: Dose escalation to the primary tumor using upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. Functional magnetic resonance imaging suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p was correlated with pulmonary toxicity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Regulatory guidance suggests capturing patient-reported overall side effect impact in cancer trials. We examined whether the Functional Assessment of Cancer Therapy (FACT) GP5 item ("I am bothered by side effects of treatment") post-neoadjuvant chemotherapy/radiotherapy differed between oxaliplatin vs. non- oxaliplatin arms in the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial of stage II-III rectal cancer patients., Methods: The R-04 neoadjuvant trial compared local-regional tumor control between patients randomized to receive 5-fluorouracil or capecitabine with radiation, with or without oxaliplatin (4 treatment arms). Participants completed surveys at baseline and immediately after chemoradiotherapy. GP5 has a 5-point response scale: "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). Logistic regression compared the odds of reporting moderate-high side effect impact (GP5 2-4) between patients receiving oxaliplatin or not after chemoradiotherapy, controlling for relevant patient characteristics. We examined associations between GP5 and other patient-reported outcomes reflecting side effects., Results: Analyses were performed among 1132 study participants. Participants receiving oxaliplatin were 1.58 times (95% CI: 1.22-2.05) more likely to report moderate-high side effect bother at post-chemotherapy/radiation. In both arms, worse overall side effect impact was associated with patient-reported diarrhea, nausea, vomiting, and peripheral sensory neuropathy (p < 0.01 for all)., Conclusion: This secondary analysis of R-04 found that GP5 distinguished between patients receiving oxaliplatin or not as part of their post-neoadjuvant chemoradiotherapy, adding patient-centric evidence on the reduced tolerability of oxaliplatin and demonstrating that GP5 is sensitive to known toxicity differences between treatments., Clinicaltrials: GOV: NCT00058474., (© 2024. The Author(s).)

Purpose: The purpose of this study was to evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer., Methods and Materials: In this phase 3, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiation therapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiation therapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiation therapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea, ≥G1 and ≥G2 diarrhea lasting at least 3 days, and damage to the rectal mucosa due to radiation therapy measured by endoscopy., Results: Two hundred and eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 142). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs 14.8 and 4.5 days, respectively; P < .001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs 55.7%, P < .001). Three patients felt intolerable or abdominal pain after rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P = .061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P < .001)., Conclusions: The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with head and neck squamous cell carcinoma (HNSCC) face several physical, emotional, and psychological challenges throughout treatment. Cisplatin-based chemoradiotherapy (CRT) is an effective but toxic treatment, with an increased risk for toxicities in patients with low skeletal muscle mass (SMM). Consequently, these patients are anticipated to experience greater treatment-related difficulties. We aimed to explore the experiences of patients with HNSCC and low SMM regarding cisplatin-based CRT., Methods: A descriptive qualitative study was conducted, interviewing seven patients 3 months after CRT using a topic guide. Thematic analysis of semi-structured interviews was conducted, to create a multi-dimensional understanding of patients' experiences during and after cisplatin-based CRT., Results: Prior to CRT themes included pre-treatment information, expectations towards treatment and trial, psychosocial circumstances, and supporting network. During CRT themes included toxicities, psychosocial impact, and supporting network. After CRT themes included reflection on period during CRT, psychosocial circumstances, informal support from networks and healthcare workers, and ongoing toxicities., Conclusion: Most patients experience cisplatin-based CRT as a life-changing and distressing life event but cope through various strategies and supporting networks. Tailored counseling, ideally with on-demand consultations, is recommended. No differences were noted in patients' perceptions of their cisplatin regimen., (© 2024. The Author(s).)

In this study, we aimed to evaluate whether the novel pretreatment Global Immune-Nutrition-Inflammation Index (GINI) can predict radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients undergoing concurrent chemoradiotherapy (CCRT). Data of LA-NPC patients presenting without RIT were reviewed retrospectively. Any post-CCRT maximum mouth openings (MMO) ≤ 35 mm were considered RIT. The GINI index was calculated using the formula: GINI = (CRP x Monocytes x Platelets x Neutrophils) ÷ (Albumin x Lymphocytes). We used receiver operating characteristic (ROC) curve analysis to examine the potential correlation between pretreatment GINI measures and post-CCRT RIT status. Logistic regression analysis examined the independence of the association between confounding factors and RIT rates. The study comprised 230 participants, and 52 (22.6%) received an RIT diagnosis. The optimal pre-CCRT GINI cutoff that dichotomizes RIT rates was determined to be 1,424 (area under the curve [AUC]: 76%; sensitivity: 75.0%; specificity: 71.7%; J-index: 0.463). RIT incidence was significantly higher in the GINI ≥ 1424 group than in its GINI < 1424 counterpart (43.3% vs. 9.3%; hazard ratio: 4.76; P < 0.001). Multivariate logistic regression analysis revealed that a pre-CCRT GINI ≥ 1424 was an independent predictor of increased RIT rates after definitive CCRT in this patient group (P < 0.001). In conclusion, the present results revealed that elevated pre-CCRT GINI measures (≥ 1424) can efficiently and independently predict elevated RIT rates in LA-NPC patients after CCRT.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Purpose: Radiation pneumonitis (RP) is a dose-limiting toxicity associated with increased mortality for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). This study aims to assess the incidence of symptomatic RP (grade 2-5), rate of recovery and associated predictive factors., Material and Methods: We performed a retrospective population-based study including 602 patients with NSCLC who were treated with CRT between 2002 and 2016. RP and rate of recovery were analysed using Common Terminology Criteria for Adverse Events version 4.0. Stepwise logistic regression was performed to analyse potential predictive factors for the two endpoints RP grade ≥ 2 and RP grade ≥ 3., Results: A total of 136 (23%) patients developed symptomatic RP and 37 (6%) developed RP grade ≥ 3. A total of 67 (71%) recovered, whereas the remaining 27 (29%), with the major proportion of patients belonging to the RP grade ≥ 3 group, suffered from prevailing sequelae. On multivariable analysis, the selected model for predicting RP grade ≥ 2 included the factors V20, smoking status, average fractions per week and chemotherapy agent. V20 and age were selected factors for RP grade ≥ 3., Interpretation: The results suggest that regardless of all proposed factors predictive for RP, the most important influenceable significant factor still is dose to the lung. The main aim should be to avoid RP grade ≥ 3, where a substantial proportion of patients suffer from prevailing sequalae. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased. e factor still is dose to the lung. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.

Background: The infection rate among patients with head-and-neck cancer (HNC) undergoing chemoradiotherapy (CRT) is approximately 19%, with sepsis-related death ranging from 3-9%. A previous study at our institute found a 12% sepsis-related death rate in HNC patients during CRT. The objective of this study is to investigate the utilization of sepsis surveillance and early intervention in reducing the occurrence of sepsis-related deaths in locally advanced HNC patients receiving CRT., Methods: This retrospective analysis examined 54 patients with locally advanced HNC undergoing CRT who underwent sepsis surveillance between January 2018 and December 2021. The study recorded the utilization of oral and intravenous antibiotics, G-CSF, early admissions and their reasons, and the incidence of early mortality. Data analysis was conducted using SPSS v.24 software., Results: Twenty-one (38.9%) patients were prescribed oral antibiotics, and 14 (25.9%) received G-CSF on an outpatient basis. Twenty-nine (54%) patients required hospital admission. Among the admitted patients, 28 (96%) received intravenous antibiotics, and G-CSF was administered in 18 (62%) patients. In 8 cases, antibiotic treatment was intensified due to persistent fever and deteriorating neutropenia. The median time for receiving antibiotics and G-CSF after starting CRT was 5th week (range: 3-8 weeks). Five patients required readmission. Only one patient succumbed to sepsis. Among the 54 patients, 48 (89%) completed the scheduled RT, while 14 (25.9%) received all 6 cycles of chemotherapy., Conclusion: Sepsis surveillance and the prompt use of antibiotics and G-CSF, along with early hospitalization, when necessary, reduces the occurrence of sepsis-related early deaths in HNC patients undergoing CRT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy., Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded., Results: A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group., Conclusions: Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin., Methods: We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI)., Results: Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range: 3.1-21.1). The mean cochlear dose (Dmc) (±SD) was 31.5 ± 8.5 Gy, and the cumulative cisplatin dose was 295 ± 50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range: 4-22) with a median audiogram follow-up of 49 months (range: 6-177). Twenty-seven patients (34%) had grades 3-4 HL. In adjusted Cox models, only higher Dmc (HR = 1.12, 95% CI:1.06-1.18) was associated with grades 3-4 HL. The predicted 3-year incidence of grades 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .78)., Conclusions: Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP., Materials and Methods: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0., Results: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively)., Conclusion: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC., (© The Author(s) 2024. Published by Oxford University Press.)

Background: In this article, we review the most recent research on probiotics effects on diarrhea in both human and animal models of the condition along with the therapeutic potential of these compounds based on their findings., Recent Findings: Nearly 50%-80% of cancer patients experience chemotherapy-induced diarrhea (CID), serious gastrointestinal toxicity of chemotherapeutic and radiation regimens that leads to prolonged hospitalizations, cardiovascular problems, electrolyte imbalances, disruptions in cancer treatment, poor cancer prognosis, and death. CID is typically categorized as osmotic diarrhea. The depletion of colonic crypts and villi by radiotherapy and chemotherapy agents interferes with the absorptive function of the intestine, thereby decreasing the absorption of chloride and releasing water into the intestinal lumen. Probiotic supplements have been found to be able to reverse the intestinal damage caused by chemo-radiation therapy by promoting the growth of crypt and villi and reducing inflammatory pathways. In addition, they support the modulation of immunological and angiogenesis responses in the gut as well as the metabolism of certain digestive enzymes by altering the gut microbiota., Conclusion: Beyond the benefits of probiotics, additional clinical research is required to clarify the most effective strain combinations and dosages for preventing chemotherapy and radiotherapy diarrhea., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Drug-radiation combination therapy is a practical approach to improving clinical outcomes for many tumours. Unfortunately, most clinical combination studies combine drugs with radiotherapy empirically and do not exploit mechanistic synergy in cell death and the interconnectivity of molecular pathways of tumours or rationale for selecting the dose, fractionation, and schedule, which can result in suboptimal efficacy and exacerbation of toxic effects. However, opportunities exist to generate compelling preclinical evidence for combination therapies from fit-for-purpose translational studies for simulating the intended clinical study use scenarios with standardised preclinical assays and algorithms to evaluate complex molecular interactions and analysis of synergy before clinical research. Here, we analyse and discuss the core issues in the translation of preclinical data to enhance the relevance of preclinical assays, in vitro clonogenic survival along with apoptosis, in vivo tumour regression and growth delay assays, and toxicology of organs at risk without creating barriers to innovation and provide a synopsis of emerging areas in preclinical radiobiology., Competing Interests: Declaration of interests PGSP, JAH, and CNC are employees of the US National Institutes of Health (NIH). MMA performed the work while employed by the NIH. All authors declare no competing interests. The opinions expressed are those of the authors and the article is compliant with NIH's manuscript publication policy., (Copyright © 2024 Published by Elsevier Ltd.)

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations., Competing Interests: Declaration of interests JMB received grants or contracts from the National Institutes of Health (NIH); royalties or licences from UpToDate; and has a leadership or fiduciary role in other board, society, committee, or advocacy group (paid or unpaid) for the American Society for Radiation Oncology (ASTRO) and is on the Board of Directors as Science Council Chair. SEF reports ongoing research with Novartis and Bayer; received consulting fees from Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; payment or honoraria as a speaker for Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; participates on an advisory board at Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid on the board of chancellors at the American College of Radiology. SKJ received grants or contracts from the National Cancer Institute, Merck, Beigene, Guardant, and Adlai made to their institution; consulting fees from Merck, AstraZeneca, Beigene, Radialogica, Syntactx, and IMX; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ASTRO; is a senior editor at the International Journal of Radiation Biology Physics; received payment for expert testimony from Dechert; support for attending meetings and travel from ASTRO, AstraZeneca, and Merck; and participation on a data safety monitoring board for Advarra. RJK declares ongoing committee role at ASTRO and ongoing senior editor role at International Journal of Radiation Oncology Biology Physics; received grants or contracts from NIH and Bridge Bio to their institution; received consulting fees from HunaTek and Guidepoint Global; has patents planned, issued, or pending with University of Wisconsin; and has leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid with ASTRO. SHL received grants from Beyond Spring, STCube Pharmaceuticals, and Nektar Therapeutics; consulting fees from XRAD Therapeutics; support for attending meetings and travel from AstraZeneca; participated on an advisory board for AstraZeneca and Creatv Microtech; and has stock or stock options from Seek Diagnostics. AMM received consulting fees from AstraZeneca, Merck, Varian Medical Systems, Kortuc, and Siemens; payment for expert testimony from Arizona Legal Group; support for attending meetings and travel from NRG Oncology; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at American Brachytherapy Society. JM declares in the last 36 months grants or contracts from NIH, Merck, BMS, Genentech, Incyte, Trisalus, Transgene, and EMD Serono; consulting fees from GLG and Guidepoint; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Association of Northern California Oncologists; participation on a data safety monitoring board or advisory board at Multiplex Thera; and stock or stock options from Multiplex Thera. SPP received grants or contracts from Amgen, AstraZeneca, MedImmune, A2bio, Bristol Myers Squibb, Eli Lilly, Fate Therapeutics, Gilead, Iovance, Merck, Pfizer, and Roche Genentech; and consulting fees from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Signatera, and Tempus. SS received grants or contracts from Merck, Regeneron, Exelixis, and Innovio; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Exelixis and Medscape; and participated on a data safety monitoring board or advisory board at Luminos, Eisai, and Naveris. MX-W received grants or contracts from NCI; consulting fees from Eli Lilly and Novocure; and participated on a data safety monitoring board or advisory board for Eli Lilly. ZSZ has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at the American Board of Radiology. KRP and PAT-S are employed by the NIH. TMW declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy., Methods: We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio., Results: Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1-5 cough, 0.176 (95%CI: 0.113-0.274, I2 = 92.36%); grades 1-5 pneumonitis, 0.118 (95%CI: 0.067-0.198, I2 = 88.64%); grades 1-5 upper respiratory tract infection, 0.064 (95%CI: 0.049-0.080, I2 = 0.98%); grades 3-5 cough, 0.050 (95%CI: 0.012-0.204, I2 = 8.90%); grades 3-5 pneumonitis, 0.052 (95%CI: 0.031-0.078, I2 = 83.86%); grades 3-5 upper respiratory tract infection, 0.040 (95%CI: 0.007-0.249, I2 = 45.31%)., Conclusions: Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients., (© 2024. The Author(s).)

Background/aim: Pneumonitis during durvalumab consolidation therapy after chemoradiotherapy (CRT) is a major cause of treatment discontinuation. Although previous studies have revealed an association between antinuclear antibody (ANA) positivity and the safety and efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC), there are no reports on durvalumab consolidation therapy. This study investigated the safety and efficacy of durvalumab after CRT in ANA-positive patients., Patients and Methods: We retrospectively reviewed patients with unresectable NSCLC treated with durvalumab after CRT between August 2018 and July 2022 at our institution. We evaluated the association among ANA positivity, treatment-related adverse events (AEs), and survival outcomes., Results: Overall, 80 patients were enrolled, 39 of whom were ANA-positive. Although there were no significant differences in the incidence of each AE of any grade, ANA-positive patients tended to have a higher frequency of pneumonitis of grade 3 to 5 than ANA-negative patients (12.8% vs. 2.4%, p=0.104). ANA-positive patients had a significantly shorter median progression-free survival (PFS) and overall survival (OS) than ANA-negative patients [14.9 months vs. not reached (NR), p=0.005; NR vs. NR, p=0.013]. Multivariate analysis revealed that ANA positivity was an independent predictor of shorter PFS (HR=2.23; 95% CI=1.16-4.29; p=0.016) and OS (HR=2.28; 95% CI=1.01-5.12; p=0.046)., Conclusion: ANA-positive patients receiving durvalumab after CRT tended to have a higher frequency of severe pneumonitis and significantly worse PFS and OS compared with ANA-negative patients., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer., Methods: We retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m 2 /week) and nedaplatin (5 mg/m 2 /day) were administered through a shallow temporal artery using a catheter., Results: In total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001)., Conclusion: IMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields., Methods: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field., Results: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons., Conclusions: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Purpose: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18 F-FDG-PET voxel intensity-based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT)., Methods and Materials: This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent., Primary Outcomes: 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm 3 can receive >84 Gy and normalized isoeffective dose >96 Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers., Results: Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P = .021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P = .1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P = .005) and alcohol users (33% vs 13%; P = .02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P = .005) and ≥G4 (29% vs 8%; P = .048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity., Conclusions: A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated., Materials and Methods: This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 10 9 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis., Results: After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A., Conclusions: CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Radiotherapy (RT) is a standard treatment for head and neck cancer (HNC) and chemoradiotherapy (CRT) is indicated for patients with locally advanced disease. Toxicities during treatment are common and can lead to early cessation of chemotherapy and radiotherapy (RT) interruptions, which can affect oncologic outcomes. Skeletal muscle mass (SMM) is a new biomarker to predict toxicities and overall survival. The aim of this systematic review is to provide an overview of studies towards the associations between SMM and dose limiting toxicity (DLT) and/or RT interruptions in HNC patients. A systematic literature search was conducted and yielded 270 studies. Inclusion criteria were articles published in English that investigated the effect of low SMM measured in humans with HNC on toxicities during CRT or RT. Studies that did not investigate oral cavity, oropharynx, larynx, hypopharynx, nasopharynx cancers or carcinoma of unknown primary were excluded. This led to the inclusion of 22 original studies. The prevalence of low SMM ranged from 19.7 % to 74.7 %. SMM was often assessed by measuring the cross-sectional muscle area at the level of the third cervical vertebra on computed tomography scans. Cut-off values used to categorize patients in SMM groups varied. In the meta-analyses heterogeneity was moderate (I 2  = 68 % and 50 % respectively). Patients with low SMM had higher, but only borderline significant, odds of DLT during CRT (OR 1.60; 95 % CI 1.00-2.58; p = 0.0512) and RT interruptions (OR 1.89; 95 % CI 1.00-3.57; p = 0.0510) compared to patients without low SMM. To conclude, in HNC patients low SMM, defined with different methods and cut-off values, is associated with DLT and RT interruptions during (C)RT, although the difference is only borderline statistically significant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC)., Methods: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD‑1 mAbs and 41 patients received sequential radiotherapy with anti-PD‑1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V 5 -V 50 , respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP., Results: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD‑1 mAbs administered concurrently with radiotherapy, V 5 , V 10 , V 15 , V 25 , V 30 , V 35 , V 40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V 5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V 5 threshold for predicting grade 2 or higher TRP was 55.7%., Conclusion: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD‑1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD‑1 mAbs administered concurrently with radiotherapy and the lung V 5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V 5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy., (© 2024. The Author(s).)

Purpose: Re-irradiation (reRT) is an effective treatment modality for patients with recurrent glioma. Data on dose escalation, the use of simulated integrated boost and concomitant therapy to reRT are still scarce. In this monocentric cohort of n = 223 patients we investigated the influence of reRT dose escalation as well as the concomitant use of bevacizumab (BEV) with regard to post-recurrence survival (PRS) and risk of radionecrosis (RN)., Patients and Methods: Patients with recurrent glioma treated between July 2008 and August 2022 with reRT with BEV, reRT with temozolomide (TMZ) and reRT without concomitant systemic therapy were retrospectively analyzed. PRS and RN-free survival (RNFS) were calculated for all patients using the Kaplan-Meier estimator. Univariable and multivariable cox regression was performed for PRS and for RNFS. The reRT Risk Score (RRRS) was calculated for all patients., Results: Good, intermediate and poor risk of the RRRS translated into 11 months, 9 months and 7 months of median PRS (univariable: p = 0.008, multivariable: p = 0.013). ReRT was applied with a dose of ≤36 Gy (n = 140) or >36 Gy (n = 83). Concomitant bevacizumab (BEV) therapy was performed in n = 122 and concomitant temozolomide (TMZ) therapy in n = 32 patients. Median PRS was 10 months in patients treated with >36 Gy and 8 months in patients treated with ≤36 Gy (univariable: p = 0.032, multivariable: p = 0.576). Regarding concomitant TMZ therapy, median PRS was 14 months vs. 9 months for patients treated with or without TMZ (univariable: p = 0.041, multivariable: p = 0.019). No statistically significant influence on PRS was seen for concomitant BEV therapy in this series. RN was less frequent for reRT with concomitant BEV, (17/122; 13.9 %) than for reRT without BEV (30/101; 29.7 %). Regarding RNFS, the hazard ratio for reRT with BEV was 0.436 (univariable; p = 0.006) and 0.479 (multivariable; p = 0.023), respectively. ReRT dose did not show statistical significance in regards to RN (univariable: p = 0.073, multivariable: p = 0.404). RNFS was longer for patients receiving concomitant BEV to reRT than for patients treated with reRT only (mean 31.7 vs. 30.9 months, p = 0.004)., Conclusion: In this cohort, in patients treated with concomitant BEV therapy RN was less frequently detected and in patients treated with concomitant TMZ longer PRS was observed. Based on these results, the best concomitant therapy and the optimal dose should be decided on a patient-by-patient basis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maximilian Niyazi has received speaker honoraria from Astra Zeneca und Brainlab. Raphael Bodensohn has received honoraria from NovoCure for participating in invited meetings of specialized centers. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy., Methods and Materials: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy., Results: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535)., Conclusions: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Radiation esophagitis is frequent and annoying toxicity in high dose thoracic radiation therapy. Contalateral esophagus sparing intensity modulated radiation therapy (CES-IMRT) has been proposed to mitigate this problem, and this is to report the impact of CES-IMRT in definitive concurrent chemoradiotherapy (dCCRT) for lung cancer patients., Materials and Methods: From January 2021 till May 2023, 183 stage III non-small cell lung cancer patients underwent dCCRT. Esophagus was located within 1 cm from internal target volume in 159 patients. We comparatively evaluated the frequency and severity of esophagitis by pain-killer usage, analgesic quantification algorithm (AQA) score, and failure patterns in 159 CES-necessary patients., Results: All patients underwent dCCRT (66 Gy in 30 fractions with concurrent chemotherapy). Actual CES-IMRT application was determined based on the discretion of responsible radiation oncologists: CES-applied in 41 patients; and CES-unapplied in 118. CES-applied patients experienced pain events less frequently (pain-killer usage: 53.7 % vs. 77.1 %, p = 0.008) and less severely (AQA score of 2-3: 39.0 % vs. 68.6 %, p = 0.002). On multivariate analyses, overlapping volume of esophagus and planning target (HR = 1.32, 95 % CI 1.12-1.55, p = 0.001) and CES-IMRT application (HR = 0.31, 95 % CI 0.13-0.76, p = 0.010) were associated with AQA score of 2-3 less frequently. There were no differences in failure pattern, progression-free survival, and overall survival., Conclusions: CES-IMRT application resulted in less frequent and less severe pain events without compromising oncologic outcomes. Further studies, preferably in a randomized fashion, would be desired., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC., Patients and Methods: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS)., Results: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature., Conclusions: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy., Methods and Materials: In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events., Results: A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups., Conclusions: Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Systemic treatments are listed as first-line therapies for HCC with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy in HCC with PVTT and to identify prognostic biomarkers., Approach and Results: This open-label, multicenter, single-arm, phase 2 clinical trial was conducted at 3 tertiary hospitals in China. A total of 46 patients with HCC with PVTT were enrolled. All the patients received the first cycle of i.v. sintilimab (200 mg, day 1) plus bevacizumab (15 mg/kg, day 1) within 3 days after enrollment. Radiotherapy (30-50 Gy/10 fractions) was administered after 2 cycles of Sin-Bev. Sin-Bev was disrupted during radiotherapy and resumed 2 weeks after radiotherapy and continued every 3 weeks thereafter until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate. Patients obtained an objective response rate of 58.7% and a disease control rate of 100%. After a median follow-up time of 26.0 months (95% CI: 24.0-26.0), the median OS was 24.0 months (95% CI: 19.0 to not applicable) and the median progression-free survival was 13.8 months (95% CI: 12.0-21.0), respectively. No unexpected adverse events or treatment-related deaths occurred. Mutations of PCTMD1 were predictive of shorter OS and progression-free survival., Conclusions: Sintilimab plus bevacizumab combined with radiotherapy provides favorable treatment response and survival outcomes along with an acceptable safety profile in the first-line setting for patients with HCC with PVTT (ClinicalTrials.gov Identifier: NCT05010434)., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: To investigate the impact of early and continuous postoperative inpatient rehabilitation during chemoradiotherapy on functional outcomes and overall survival (OS) in patients with glioblastoma (GBM), particularly in different age groups., Methods: This retrospective cohort study at a university hospital (2011-2016) included 75 of 119 consecutive patients newly diagnosed with GBM who underwent standardized treatment and postoperative rehabilitation. Patients were divided into older (≥ 65 years, n = 45) and younger (< 65 years, n = 30) groups, engaging in a 50-day rehabilitation program. We assessed rehabilitation progress, Barthel Index (BI), Brunnstrom Recovery Stage (BRS), adverse events, and OS. BI at discharge and survival were analyzed using multivariate and Cox regression models, respectively., Results: The mean age was 72.5 ± 6.3 and 52.4 ± 7.8 years in the older and younger groups, respectively. Both groups demonstrated significant improvements in BI and BRS. Despite more adverse events in the older group, no significant difference existed in median OS (older group: 18.7 months vs. younger group: 18.3 months, p = 0.87). Early walking training, reduced fatigue during chemoradiotherapy, and high Karnofsky Performance Status at admission significantly impacted the BI at discharge. Cox regression analysis identified the BI at discharge as a significant predictor of survival (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.97-0.99, p = 0.008)., Conclusion: Integrated rehabilitation improves functional outcomes, and enhanced ADL at discharge is associated with improved survival outcomes in patients with GBM, regardless of age. This highlights the need for personalized rehabilitation in treatment protocols. Further prospective studies are warranted to confirm these findings., (© 2024. The Author(s).)

Background and Purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data., Materials and Methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism., Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism., Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This systematic review (PROSPERO: CRD4202345740) identified and synthesised existing evidence on nutrition interventions performed by healthcare professionals, and the contents of the interventions that prevented weight loss in patients with HNC undergoing RT/CRT., Methods: We included quantitative studies. PubMed, CINAHL, Cochrane Library, and Scopus were searched, and the outcomes of interest were weight change and nutritional status. A narrative synthesis was undertaken to elaborate on the findings across the included studies. Furthermore, a meta-analysis was conducted., Results: A total of 27 studies were identified. Most focused on the effect of oral nutritional supplements (ONS) and individualised nutrition counselling (INC). A beneficial effect of ONS combined with weekly INC were identified, and compliance, management of adverse effects, involvement of family as well as the knowledge and approach of the healthcare professionals were identified as key elements when supporting the management of nutrition intake in HNC patients during RT/CRT. The meta-analysis showed a non-significant effect of ONS, yet significant when combined with INC, and no overall effect of INC, but significant effect in the RCTs., Conclusion: Our results suggest an optimal effect of ONS combined with weekly INC, requiring a focus on enhancing compliance as well as support from a multidisciplinary team to manage adverse treatment effects. Compliance must be emphasised to provide maximum support to the patient, as well as focus on the knowledge of the health care professionals performing the intervention. Further research on strategies to enhance patient compliance and involvement is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinomas of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA., Purpose: To investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity., Material/methods: Patients were treated with RT and weekly cisplatin 40 mg/m2 between 1998-2020. Retrospective data from medical records (n=65) and prospectively collected data from an observational study (n=51) comprising physician assessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2-4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method., Results: We included 116 patients. T-stages were T1:4%, T2: 71%, T3: 17%, T4: 8% and 47% has N+ disease. RT doses were 53.75-64 Gy/45-51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77% (95%CI 68.7;84.5%) and 86.4% (95%CI 78.3;91.7%), respectively. Hospitalization occured in 20% with 2.6% being admitted due to febrile neutropenia. Hematological toxicity was low with 13.7% grade 3 and 3.9% grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild., Conclusion: RT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To evaluate the predictive potency of a novel index combining the pan-immune-inflammatory index and hemoglobin levels (PIV/Hb) for the prevalence of radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal cancer (LA-NPC) receiving concurrent chemoradiotherapy (CCRT)., Methods: Data from 228 LA-NPC patients were retrospectively examined. Maximum mouth openings (MMO) were measured to confirm the presence of RIT, defined as MMOs ≤35 mm. Complete blood test results from the first day of CCRT were used to calculate PIV/Hb levels. A potential relationship between pretreatment PIV/Hb and the RIT status was evaluated using receiver operating characteristic (ROC) curve analysis., Results: Post-CCRT RIT was diagnosed in 20.2% of the patients. The ROC curve analysis determined 68.4 g/dL as the ideal PIV/Hb cutoff that effectively divided patients into two distinct groups (area under the curve: 94.7%; specificity: 86.4%; sensitivity: 87.4%). RIT was significantly more prevalent in the PIV/Hb > 68 group than in the PIV/Hb < 68 group (58.8% vs. 3.8%; P < 0.001). Multivariate logistic regression analysis showed that a pre-CCRT PIV > 68 was independently associated with significantly higher rates of RIT., Conclusion: Higher pretreatment levels of the novel PIV/Hb index predict increased RIT rates following definitive CCRT for LA-NPCs., Competing Interests: The authors declare that they have no conflicts of interest. The authors have not entered into any agreements that would hinder our access to the research data, independent analysis, manuscript preparation, or publication., (Copyright © 2024 Efsun Somay et al.)

Background: In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC., Methods: This single-arm, phase-II trial enrolled operable T3-4N0-2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy., Results: In a total of 30 patients in the intention-to-treat (ITT) population, grades 3-4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8 + T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8 + CD39 + T cells and lower HLA-DR + Tregs., Conclusions: Neoadjuvant IPI-NIVO-CRT in T3-4N0-2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs., Trial Registration Number: NCT04245514., Competing Interests: Competing interests: The authors have disclosed the following conflicts of interest: DEO-L received grants from Janssen and Curium, honoraria from EANM, EAU, ESMO, and Curium, travel support from EANM, ESMO, EAU, and Bayer, and serves on a Bayer advisory board. CD received institutional fees for advisory roles with BMS, AstraZeneca, and MSD. SMSH has research contracts with several pharmaceutical companies and received honoraria from Janssen. IB’s institution received support from BMS, AstraZeneca, and Boehringer Ingelheim, and he received honoraria from AstraZeneca, MSD, and BMS. FLS received a research grant from ViewRay and honoraria from AstraZeneca. SS’s institution received grants from Varian, ViewRay, and AstraZeneca; he received consulting fees and honoraria from AstraZeneca and MSD, and serves on advisory boards for AstraZeneca and MSD. TDdG’s institution received grants from Idera Pharmaceuticals, consulting fees from LAVA Therapeutics and Mendus, and she holds stock in LAVA Therapeutics. All other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This qualitative study explored patients' experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT)., Setting: Recruitment at five clinical sites in England and Wales, UK., Participants: SCOPE2 trial participants were invited to take part in interviews from across five clinical sites. Participants self-selected to take part in up to three interviews across four different time points: baseline (before treatment) and at 2-3 months, 3-6 months or 6 months+ after baseline. There were five female and five male interview participants., Interventions: Participants were randomised to standard dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine, or an escalated dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine., Methods: This qualitative study used semistructured longitudinal interviews to explore the impact of treatment on patient outlook and quality of life and the impact of the COVID-19 pandemic. Interview data were thematically analysed., Results: 10 patients participated in 16 longitudinal interviews. Three participants were accompanied by companions. Participants experienced side-effects from radiotherapy and chemotherapy including nausea, throat pain, difficulties eating and regaining appetite, thrombosis and fatigue, although most of these symptoms gradually improved. Participants required more ongoing information and support regarding treatment side-effects and cancer status in order to improve their overall quality of life. Best practice examples involved key contacts providing practical advice and signposting support., Conclusion: Participants of the SCOPE2 trial reported short and longer-term side-effects from chemoradiotherapy, but these usually lessened over time. Participants attempted to be positive about their survival prospects by readjusting their expectations, priorities and lifestyles. Providing patients with ongoing opportunities to discuss detailed and timely information regarding treatment side-effects, aftercare and cancer status could improve the overall health and well-being of patients during oesophageal cancer trials and pathways., Trial Registration Number: NCT02741856; ISRCTN: 97125464., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Radiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs)., Methods: We comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses., Results: Three RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58-0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P =0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P =0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P= 0.004) in terms of any grade immunotherapy-related AEs., Conclusions: CCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Ruan, Fang, Liu and Liao.)

Background: The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC., Patients and Methods: From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT., Results: A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference ( p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively ( p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group., Conclusions: Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group., (© 2024 Ayako Shiono et al., published by Sciendo.)

Purpose: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC)., Methods: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups., Results: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema., Conclusion: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen., (© 2024. The Author(s).)