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Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan–Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0–43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0–27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5–40.8) for patients with cervical tumors, 10.9 months (95% 0.0–23.2) for irresectable disease, 28.2 months (95% CI 12.3–44.0) for unfit patients, and 22.9 months (95% CI 15.4–30.5) for patients' preference for dCRT (P  = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery‐based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery‐based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. Methods Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. Results The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3‐year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681–2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3‐year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). Conclusions There was no clear difference in survival outcome between surgery‐based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

Surgery after neoadjuvant chemoradiotherapy remains the gold standard for the treatment of resectable esophageal cancer (EC); however, chemoradiotherapy without surgery has been recommended in specific cases. The aim of this meta-analysis is to analyse the survival between surgeries after neoadjuvant chemoradiotherapy compared with definitive chemoradiotherapy in order to provide a theoretical basis for clinically individualised differential treatment. We conducted an initial search of MEDLINE (PubMed), the Cochrane Library, and Embase for English-only articles that compared treatment regimens and provided survival data. According to the final I2 value of the two survival indicators, the random effect model or fixed effect model was used to calculate the overall hazard ratio (HR) and 95% confidence intervals (CI). Cochrane's Q test was used to judge the heterogeneity of the studies, and a funnel plot was used to evaluate for publication bias. A sensitivity analysis was performed to verify the stability of the included studies. A total of 38 studies involving 29161 patients (neoadjuvant therapy: 15401, definitive chemoradiotherapy: 13760) were included in the analysis. The final pooled results (HR = 0.74, 95% CI: 0.67–0.82) showed a statistically significant increase in overall survival with neoadjuvant chemoradiotherapy plus surgery compared with definitive chemoradiotherapy. Subgroup analyses were performed to determine the effects of heterogeneity, additional treatment regimens, study types, and geographic regions, as well as histologic differences, complications, and recurrence, on the overall results. For people with esophageal cancer that can be removed, neoadjuvant chemoradiotherapy combined with surgery improves survival compared to definitive chemoradiotherapy. However, more research is needed to confirm these results and help doctors make decisions about treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of chemoradiotherapy followed by surgery (trimodality therapy) is considered standard of care for patients with locally advanced esophageal adenocarcinoma, but many potential candidates for surgery receive curative-intent chemoradiotherapy alone. This study compared the outcomes of patients who received trimodality therapy to those who received curative-intent chemoradiotherapy. Our primary analysis found that trimodality therapy reduced the risk of local tumor recurrences, but we did not detect statistically significant differences in the risks of distant metastases or mortality. These results can help patients and clinicians make informed treatment decisions, although further studies are needed to refine our understanding of the trade-offs between the two treatment strategies. The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24–0.62; p < 0.001 ) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77–1.91; p = 0.40 ). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56–1.09; p = 0.14 ) or cancer-specific survival (HR, 0.83; 95% CI, 0.57–1.21; p = 0.33 ). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Recent developments in esophageal cancer treatment, including studies exploring active surveillance following chemoradiotherapy, have led to a need for clear terminology and definitions regarding different multimodal treatment options. Objective: The aim of this study was to reach worldwide consensus on the definitions and semantics of multimodal esophageal cancer treatment. Methods: In total, 72 experts working in the field of multimodal esophageal cancer treatment were invited to participate in this Delphi study. The study comprised three Delphi surveys sent out by email and one online meeting. Input for the Delphi survey consisted of terminology obtained from a systematic literature search. Participants were asked to respond to open questions and to indicate whether they agreed or disagreed with different statements. Consensus was reached when there was ≥75% agreement among respondents. Results: Forty-nine of 72 invited experts (68.1%) participated in the first online Delphi survey, 45 (62.5%) in the second survey, 21 (46.7%) of 45 in the online meeting, and 39 (86.7%) of 45 in the final survey. Consensus on neoadjuvant and definitive chemoradiotherapy with or without surgery was reached for 27 of 31 items (87%). No consensus was reached on follow-up after treatment with definitive chemoradiotherapy. Conclusion(s): Consensus was reached on most statements regarding terminology and definitions of multimodal esophageal cancer treatment. Implementing uniform criteria facilitates comparison of studies and promotes international research collaborations. [ABSTRACT FROM AUTHOR]

Background: The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery‐based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery‐based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. Methods: Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. Results: The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3‐year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681–2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3‐year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). Conclusions: There was no clear difference in survival outcome between surgery‐based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients. [ABSTRACT FROM AUTHOR]

Summary: Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I–IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8–46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9–62.8) and 35.7% (95% CI 23.8–53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43–42.54, P

This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression‐free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p < 0.001). Patients with concurrent CRT demonstrated markedly improved PFS (p = 0.012) and OS (p = 0.017) than those undergoing sequential CRT. Additionally, those with a programmed‐death ligand 1 (PD‐L1) expression of 50% or higher showed significantly elevated ORRs (72.2% vs. 47.2%, p = 0.011) and superior OS (median 44.8 vs. 28.6 months, p = 0.004) compared to patients with PD‐L1 expression below 50%. Hematologic toxicities were the primary severe adverse events (grade ≥ 3) encountered, with no unforeseen treatment‐related toxicities. Thus, induction immunochemotherapy followed by definitive CRT demonstrated encouraging efficacy and tolerable toxicities for unresectable LA‐NSCLC. [ABSTRACT FROM AUTHOR]

Introduction. Sporadic cases of squamous cell carcinoma of the rectum (rSCC) do not allow a comparative characterization of tumor aggressiveness and its response to chemoradiotherapy in relation to more common squamous cell entities, in particular, anal squamous cell carcinoma (aSCC). Objective: comparative evaluation of the short- and long-term results of chemoradiation therapy in patients with rSCC and aSCC. Material and Methods. In this retrospective study we included patients with nonmetastatic squamous cell carcinoma of the rectum (rSCC) and anal canal squamous cell carcinoma (aSCC) who received chemoradiotherapy and compared them in a 1:1 ratio using propensity-score matching. The dynamics of tumor response to treatment were compared by Kaplan-Meier survival analysis (OS and RFS) followed by Log-Rank verifcation, rate of complete response after 6 months. Results. A total of 15 pairs of matched patients were evaluated. Patients in both groups had reliably similar sex, age, histological grade, initial primary tumor size, differing only in tumor histological subtype. In the aSCC group, 60 % of patients had metastases to pelvic lymph nodes, while in the rSCC group metastases had 46.67 % (p=1). The median follow-up was 44 months. The 3-year OS in the aSCC group of patients was 76.9 %, and 71.4 % in the rSCC group (p=0.567). The 3-year DFS in the aSCC group was 66.7 %, and in the rSCC group 34.7 % (p=0.406). The rate of achieving complete clinical response to CRT after 6 months was 86.7 % for the aSCC group and only 46.7 % for the rSCC group (p=0.05). Organ-saving treatment was achieved in 93.3 % of aSCC patients and 73.3 % of rSCC patients (p=0.33). Conclusion. Overall and recurrence-free survival rates were not signifcantly decreased for rSCC patients relative to aSCC patients. This indicates a similar course and prognosis in the two diseases, but rSCC is characterized by a signifcantly lower rate of complete response to treatment.

Abstract This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression‐free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p

Objective The aim of this study is to determine prognostic values of sequential 18 F-FDG PET/CT metabolic parameters in locally advanced esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy. Materials and Methods Forty locally advanced ESCC patients treated with definitive chemoradiotherapy (dCRT) who received pre-treatment 18 F-FDG PET/CT (PET1) and 3-months post-treatment 18 F-FDG PET/CT (PET2) were enrolled in the prospective study. 18 F-FDG PET parameters of the primary tumor including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated on PET delineated primary tumor. Using Kaplan-Meier curves to estimated overall survival (OS), progression-free survival (PFS), and local-regional control (LRC). Cox regression analysis was performed to find significant prognostic factors for survival. Results With a median follow-up of 13.5 months, the 4-year OS, PFS, and LRC rates were 67.3%, 52.6%, and 53.4% respectively. Patients with MTV 2 > 5.7 had lower OS, PFS, and LRC rates than the lower MTV 2 group (p < 0.05). Univariate Cox regression analysis showed that MTV2 was a significant prognostic factor for OS, PFS, and LRC (p < 0.05). Conclusion MTV parameter of sequential 18 F-FDG PET/CT could be used as a prognostic factor for OS, PFS, and LRC in locally advanced ESCC patients treated with dCRT. [ABSTRACT FROM AUTHOR]

Background To investigate the association between absolute lymphocyte count (ALC) nadir and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, as well as to explore clinical characteristics and dosimetric parameters that affect ALC nadir during CRT. Patients and Methods Patients with ESCC (n = 602) who underwent definitive CRT were analyzed, of whom 166 received combined anti-PD-1 immunotherapy and CRT. Changes in ALC and survival were compared between patients with and without immunotherapy. Propensity score matching (PSM) was performed to minimize the effects of confounding factors. Low ALC was defined as nadir of <0.33 × 103 cells/μL during CRT (top tertile). Univariate and multivariate logistic regression were used to identify predictors of low ALC nadir. Results Patients with immunotherapy had significantly higher ALC in the first 3 weeks during CRT and higher ALC nadir than those without. Overall survival was more favorable in patients with immunotherapy both before and after PSM. After a median follow-up of 12.1 months, patients with low ALC during CRT had a worse progression-free survival (PFS) (P =.026). In multivariate analysis, low ALC remained a significant prognostic factor for PFS. Planning target volume (PTV) and heart V5 were revealed to be independent predictors of low ALC. Conclusions The addition of anti-PD-1 immunotherapy to definitive CRT could mitigate the decline of ALC during radiotherapy and might prolong survival. Low ALC nadir was correlated to worse PFS, larger PTV, and higher heart V5 in patients receiving combined immunotherapy and CRT. [ABSTRACT FROM AUTHOR]

Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot‐assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73‐year‐old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0‐Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation. [ABSTRACT FROM AUTHOR]

Abstract Objective: The efficacy and safety of definitive chemoradiotherapy (dCRT) for elderly patients with unresectable esophageal cancer (EC) are not yet fully understood. We conducted this study to evaluate the outcome and toxicity in elder patients (65 years and over) of unresectable EC treated with dCRT. Methods: From four Georgian cancer centers with a radiation oncology department, we identified 44 elderly patients with EC suitable according to the study criteria. Overall survival (OS) was estimated from the beginning of treatment and toxicity scored using CTCAE 5.0 criteria. Results: The median age of patients was 70.0 years (range 65–83 years), with male predominance (77.3%) and 59% of patients were with Eastern Cooperative Oncology Group (ECOG) performance status 1. Because of significant dysphagia (grade 3–4) nine patients underwent intervention (stenting or gastrostomy) before dCRT. More than two‐thirds of patients were squamous cell histological type (77.3%). Localization of tumors was equally distributed between the middle and lower parts of the esophagus (38.6%) and in 26 patients (59.1%) tumor length was more than 5 cm. The majority of patients had stage III disease (61.4%). Median survival was 16.0 months (95% confidence interval [CI] 0–35.9). OS at 12 and 24 months was 53.7% and 43.6%, respectively. Fifteen patients (34%) were alive from 2.1 to 5.4 years after treatment. A statistically significant difference (p = 0.011) in median OS was found between patients who received full (not reached) versus overall survival (OS) was 9.0 months in patients who received nonfull dose of radiotherapy (RT) (95% CI 2.79–15.2). Additional analysis between age subgroups revealed that elder subgroup patients (>75 years) had the highest OS, compared to younger (65–70 years) and intermediate groups (71–75 years) (p = 0.001). The most common adverse events were grade 3–4 leukopenia (43.2%), anemia (29.5%), and esophagitis (27.3%). Conclusion: The results of our study support the feasibility and efficacy of dCRT for unresectable EC in carefully selected elderly patients. Survival was correlated to complete dose of RT and therefore accurate selection of patients is crucial for better long‐term survival. Our study showed that chronological age alone does not reflect a patient's ability to tolerate dCRT. Toxicity of dCRT is always a very important issue and patient selection must be very cautious in geriatric patients, although dCRT might benefit highly selected patients.

Abstract Objective: The aim of this study is to report the survival and treatment results of patients with cervical esophageal cancer treated with definitive chemoradiotherapy, whose incidence is very low in the population and there is not enough information about treatment and toxicity results in the literature. Material and Method: Between 2013 and 2022, 10 patients (six males and four females) with cervical esophageal cancer treated with definitive chemoradiotherapy were included. Among these patients, seven had stage II disease, one stage III, and 2 stage IVA. All patients received radiotherapy at a median dose of 50.4 Gy and concurrent weekly chemotherapy. Results: The median follow-up period was 18 months. The two-year and 5-year overall survival rates were 42.2% and 21.1%, respectively. The two-year and 5-year disease-free survival rates were 45.7% and 22.9%, respectively. Disease progression was noted in 3 out of 10 patients (30%). Three patients were still alive during analyze. Percutaneous enteral gastrostomy was performed in 3 of 10 patients. These requirement occured in 1 due to local progression, and in the remaining 2 patients due to the side effect of RT. Conclusions: Overall survival rates were low, as similar findings appear in the literature. It was remarkable that the need for a percutaneous enteral gastrostomy was not observed in the IMRT group. All patients with complete remission were in stage 2.

Abstract Background With the improved survival rate of patients with esophageal cancer, secondary cancers, including pharyngolaryngeal cancer, have become a problem. Phanryngolaryngeal cancer surgery often requires esophagogastric anastomosis resection in patients with a previous history of subtotal esophagectomy. Owing to adhesions, especially surrounding the esophagogastric anastomosis, caused by the initial surgery, the second surgery might cause postoperative complications. Case presentation A 65-year-old man was diagnosed with early stage esophageal squamous cell carcinoma and underwent endoscopic mucosal dissection. However, the histopathological depth of the tumor was pT1b, and additional treatment was required. After administration of the neoadjuvant chemotherapy, he underwent thoracoscopic esophagectomy and retrosternum reconstruction via a gastric tube (pT1N3M0 stage III). Eight months after the first surgery, tumor recurrences were observed at the anastomosis and left cervical lymph node. Definitive chemoradiotherapy was performed for the recurrences, and complete response was achieved. Seven months after chemoradiotherapy, he was diagnosed with hypopharyngeal squamous cell carcinoma in the right piriform fossa (cT2N2bM0 stage IVA), and salvage surgery was chosen as treatment. The surgical findings revealed strong adhesion around the remnant esophagus, which was difficult to dissect from surrounding tissue and was associated with a risk of breaking of the anastomosis. However, indocyanine green fluorescence imaging findings indicated sufficient blood flow to preserve the remnant esophagus, including the anastomosis, even after the interruption of blood flow from the proximal side of the esophagus by total pharyngolaryngectomy. Finally, approximately 4 cm of the remnant esophagus was preserved, and the free jejunum reconstruction with cervical vascular anastomosis was performed. Moreover, the patient was discharged without complications on postoperative day 38. After 10 months of the second surgery, a metastatic lymph node was observed in the right neck. Immune checkpoint inhibitors and chemotherapy were administered, and the patient is alive and under treatment 1.5 years after the second surgery. Conclusions Blood supply to the remnant cervical esophagus was thought to be from the gastric conduit over the anastomosis and surrounding capillaries. Thus, the preservation of the remnant esophagus can be considered in total pharyngolaryngectomy even after

Primary lung cancer is the most common cancer worldwide and is an increasingly common problem. The primary endpoint of this study was; to investigate the effect of radiotherapy dose and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and progression-free survival (PFS). We retrospectively examined 99 patients who were stage III A and stage III B at the time of diagnosis, who did not receive surgical treatment, and who received definitive chemoradiotherapy. Data of patients such as sex, age, ECOG status, tumor location, pathological subtype, radiotherapy dose, type of chemotherapy, neutrophil/lymphocyte ratio (NLR), and some biochemical parameters and PFS and OS were included in the study by scanning the patient's files. The radiotherapy cut-off value was accepted as 60 Gray. OS was statistically better in patients who received radiotherapy at doses of 60 Gray and above. When the patients with radiotherapy dose less than 60 Gy and patients with more than 60 Gray were evaluated in two groups, the overall survival was 8,569 ± 1,404 / month and 14,326 ± 1,209 / month, respectively. (p 4 was 14.32 ± 1.30 / month and 10.54 ± 1.16 / month, respectively. (p

Simple Summary: Salvage lung resection for lung cancer is a relatively new concept, and most of the operated patients present non-small cell lung cancer (NSCLC). For small-cell lung cancer (SCLC), salvage surgery is extremely rarely performed, in highly selected patients proved with limited disease after radical chemoradiation, as an alternative to second-line chemotherapy. From the published cases, it appeared that salvation surgery for SCLC presents postoperative morbidity similar to salvage surgery for NSCLC, no postoperative mortality, and a median estimated overall survival of 92% at 2 years and 66% at 5 years. Salvage lung resection for SCLC may be a reasonable treatment in very highly selected patients, offering good local control and a favorable survival outcome. (1) Background: Salvation surgery for small-cell lung cancer (SCLC) is exceptionally performed, and only a few cases are published. (2) Methods: There are 6 publications that present 17 cases of salvation surgery for SCLC—the salvation surgery was performed in the context of modern clearly established protocols for SCLC and after including SCLC in the TNM (tumor, node, metastasis) staging in 2010. (3) Results: After a median follow-up of 29 months, the estimated overall survival (OS) was 86 months. The median estimated 2-year survival was 92%, and the median estimated 5-year survival was 66%. (4) Conclusion: Salvage surgery for SCLC is a relatively new and extremely uncommon concept and represents an alternative to second-line chemotherapy. It is valuable because it may offer a reasonable treatment for selected patients, good local control, and a favorable survival outcome. [ABSTRACT FROM AUTHOR]

Abstract Background The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options. Methods We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed. Results A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS. Conclusion We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.

Background: With the improved survival rate of patients with esophageal cancer, secondary cancers, including pharyngolaryngeal cancer, have become a problem. Phanryngolaryngeal cancer surgery often requires esophagogastric anastomosis resection in patients with a previous history of subtotal esophagectomy. Owing to adhesions, especially surrounding the esophagogastric anastomosis, caused by the initial surgery, the second surgery might cause postoperative complications. Case presentation: A 65-year-old man was diagnosed with early stage esophageal squamous cell carcinoma and underwent endoscopic mucosal dissection. However, the histopathological depth of the tumor was pT1b, and additional treatment was required. After administration of the neoadjuvant chemotherapy, he underwent thoracoscopic esophagectomy and retrosternum reconstruction via a gastric tube (pT1N3M0 stage III). Eight months after the first surgery, tumor recurrences were observed at the anastomosis and left cervical lymph node. Definitive chemoradiotherapy was performed for the recurrences, and complete response was achieved. Seven months after chemoradiotherapy, he was diagnosed with hypopharyngeal squamous cell carcinoma in the right piriform fossa (cT2N2bM0 stage IVA), and salvage surgery was chosen as treatment. The surgical findings revealed strong adhesion around the remnant esophagus, which was difficult to dissect from surrounding tissue and was associated with a risk of breaking of the anastomosis. However, indocyanine green fluorescence imaging findings indicated sufficient blood flow to preserve the remnant esophagus, including the anastomosis, even after the interruption of blood flow from the proximal side of the esophagus by total pharyngolaryngectomy. Finally, approximately 4 cm of the remnant esophagus was preserved, and the free jejunum reconstruction with cervical vascular anastomosis was performed. Moreover, the patient was discharged without complications on postoperative day 38. After 10 months of the second surgery, a metastatic lymph node was observed in the right neck. Immune checkpoint inhibitors and chemotherapy were administered, and the patient is alive and under treatment 1.5 years after the second surgery. Conclusions: Blood supply to the remnant cervical esophagus was thought to be from the gastric conduit over the anastomosis and surrounding capillaries. Thus, the preservation of the remnant esophagus can be considered in total pharyngolaryngectomy even after < 2 years of esophagectomy by blood flow evaluation using indocyanine green fluorescence. [ABSTRACT FROM AUTHOR]

Objective: The efficacy and safety of definitive chemoradiotherapy (dCRT) for elderly patients with unresectable esophageal cancer (EC) are not yet fully understood. We conducted this study to evaluate the outcome and toxicity in elder patients (65 years and over) of unresectable EC treated with dCRT. Methods: From four Georgian cancer centers with a radiation oncology department, we identified 44 elderly patients with EC suitable according to the study criteria. Overall survival (OS) was estimated from the beginning of treatment and toxicity scored using CTCAE 5.0 criteria. Results: The median age of patients was 70.0 years (range 65–83 years), with male predominance (77.3%) and 59% of patients were with Eastern Cooperative Oncology Group (ECOG) performance status 1. Because of significant dysphagia (grade 3–4) nine patients underwent intervention (stenting or gastrostomy) before dCRT. More than two‐thirds of patients were squamous cell histological type (77.3%). Localization of tumors was equally distributed between the middle and lower parts of the esophagus (38.6%) and in 26 patients (59.1%) tumor length was more than 5 cm. The majority of patients had stage III disease (61.4%). Median survival was 16.0 months (95% confidence interval [CI] 0–35.9). OS at 12 and 24 months was 53.7% and 43.6%, respectively. Fifteen patients (34%) were alive from 2.1 to 5.4 years after treatment. A statistically significant difference (p = 0.011) in median OS was found between patients who received full (not reached) versus overall survival (OS) was 9.0 months in patients who received nonfull dose of radiotherapy (RT) (95% CI 2.79–15.2). Additional analysis between age subgroups revealed that elder subgroup patients (>75 years) had the highest OS, compared to younger (65–70 years) and intermediate groups (71–75 years) (p = 0.001). The most common adverse events were grade 3–4 leukopenia (43.2%), anemia (29.5%), and esophagitis (27.3%). Conclusion: The results of our study support the feasibility and efficacy of dCRT for unresectable EC in carefully selected elderly patients. Survival was correlated to complete dose of RT and therefore accurate selection of patients is crucial for better long‐term survival. Our study showed that chronological age alone does not reflect a patient's ability to tolerate dCRT. Toxicity of dCRT is always a very important issue and patient selection must be very cautious in geriatric patients, although dCRT might benefit highly selected patients. [ABSTRACT FROM AUTHOR]

Abstract Purpose This trial aims to explore the efficacy and safety of involved-field irradiation (IFI) combined with paclitaxel plus cisplatin as concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). Methods Enrolled patients with locally advanced ESCC were treated with definitive concurrent chemoradiotherapy. IFI was administered adopting IMRT and the total dose was 61.2 Gy delivered in 34 fractions. On the first day of radiotherapy, the patients were treated with paclitaxel and cisplatin one cycle per month for 2 cycles followed by the same regimen in consolidation chemotherapy for two cycles. The primary endpoint of the study was the 2-year locoregional recurrence-free survival (LRFS) rate, and secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. Results Between January 2018 and September 2020, 108 patients participated in the trial. 78.7% (85/108) of patients completed all 4 cycles of chemotherapy. The median follow-up of the surviving patients was 33.9 months (interquartile range, 29.2–41.1). The 2-year LRFS rate, as the primary endpoint, was 64.2%. In addition, the median PFS was 39.2 months, and 1-year and 3-year OS rates of 88.0% and 63.3%, respectively. Among the patients, out-of-field regional failure was seen in only 7 (6.5%) patients. Neutropenia grade 3 and 4 occurred in 21.3% and 37.0% of the patients, respectively. Conclusions IFI using IMRT combined with paclitaxel and cisplatin concurrent chemotherapy for locally advanced ESCC yields encouraging local control and overall survival, but high hematological toxicity. Trial registration Clinical Trials ChiCTR1800017039.

Primary lung cancer is the most common cancer worldwide and is an increasingly common problem. The primary endpoint of this study was; to investigate the effect of radiotherapy dose and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and progression-free survival (PFS). We retrospectively examined 99 patients who were stage III A and stage III B at the time of diagnosis, who did not receive surgical treatment, and who received definitive chemoradiotherapy. Data of patients such as sex, age, ECOG status, tumor location, pathological subtype, radiotherapy dose, type of chemotherapy, neutrophil/lymphocyte ratio (NLR), and some biochemical parameters and PFS and OS were included in the study by scanning the patient's files. The radiotherapy cut-off value was accepted as 60 Gray. OS was statistically better in patients who received radiotherapy at doses of 60 Gray and above. When the patients with radiotherapy dose less than 60 Gy and patients with more than 60 Gray were evaluated in two groups, the overall survival was 8,569 ± 1,404 / month and 14,326 ± 1,209 / month, respectively. (p <0.05). When we evaluate the patients based on NLR; It was observed that the overall survival of patients below NLR 4 at the time of diagnosis was statistically significantly better. The overall survival of patients with NLR <4.0 and NLR> 4 were 14.32 ± 1.30 / month and 10.54 ± 1.16 / month, respectively. (p <0.05). [ABSTRACT FROM AUTHOR]

Background: Previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to definitive chemoradiotherapy (CRT) failed to significantly improve the response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report long-term results and exploratory analyses to further evaluate the therapeutic value of IC., Methods: Patients with previously untreated, unresectable, stage II-IVA ESCC were randomly assigned to receive IC followed by CRT or CRT alone. The relationship between tumor response to IC and long-term survival was analyzed. Baseline tumor biopsies were collected for RNA-Seq to identify patients who may benefit from IC., Results: Eligible patients were randomized to either the IC + CRT group (n = 55) or the CRT group (n = 55). With a median follow-up of 74.9 months, the 5-year overall survival rate was 31.8% in the IC + CRT group and 29.1% in the CRT group (P =.675; HR, 0.91; 95% CI, 0.58-1.43). Similarly, no significant differences were identified in 5-year progression-free survival between groups (30.5% vs 25.5%, P =.508; HR, 0.86; 95% CI, 0.56-1.34). Patients who responded to IC had significantly better survival than nonresponders. A risk-score model incorporating 6 key genes to predict IC efficacy was also constructed., Conclusions: Compared with definitive CRT alone, the addition of IC before CRT still failed to demonstrate superior survival in patients with unselected ESCC, based on long-term follow-up. However, because IC responders were associated with more favorable survival, potential molecular biomarkers were identified for selection of benefit population from IC., Clinical Trials Registration: NCT02403531., (© The Author(s) 2024. Published by Oxford University Press.)

Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan-Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0-43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0-27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5-40.8) for patients with cervical tumors, 10.9 months (95% 0.0-23.2) for irresectable disease, 28.2 months (95% CI 12.3-44.0) for unfit patients, and 22.9 months (95% CI 15.4-30.5) for patients' preference for dCRT (P = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Abstract Background The optimal definitive chemotherapy regimen during concurrent chemoradiotherapy (CRT) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of conflicting evidence. This study aimed to compare the effectiveness of taxane‐based chemotherapy with that of conventional cisplatin plus 5‐fluorouracil (PF) as the chemotherapy regimen in definitive CRT for ESCC. Patients and Methods This retrospective study included patients with ESCC who received paclitaxel plus carboplatin (PC) or PF during definitive CRT between May 2012 and February 2015 in a medical center in Taiwan. Survival outcomes were compared after adjustment for risk factors. Results Overall, 229 patients were evaluated. Patients in the PC group had an objective response rate of 71.1% compared with the 51.4% of the PF group (p = 0.016). The PC group showed a significantly longer progression‐free survival (PFS, p = 0.002) and overall survival (OS, p = 0.019) than the PF group. Salvage surgery also helped prolong both the PFS and OS (p

• More than 40% of patients with esophageal squamous cell carcinoma (ESCC) exhibit pathological complete responses after neoadjuvant chemoradiotherapy (nCRT), and theoretically, active surveillance could be feasible in these patients. • Compared with nCRT followed by surgery, definitive chemoradiotherapy was associated with equal survival for patients with ESCC who achieved clinical complete responses to induction chemoradiotherapy according to our criteria. • Clinical response evaluation in our study predicted postoperative pathological response with a higher accuracy which results in an overall accuracy of 86.1%. More than 40% of patients with esophageal squamous cell carcinoma (ESCC) exhibit pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (nCRT), and theoretically, these patients may be cured by CRT and omit surgery. This prospectively randomized pilot study compared definitive chemoradiotherapy (dCRT) with nCRT in patients with locally advanced ESCC who achieved clinical complete responses (cCRs) to nCRT. Single center, randomized, open phase 2 study of 256 patients with locally advanced ESCC enrolled between April 2016 and November 2018. Immediately when nCRT finished, patients enrolled underwent response evaluations within 1 week. Patients with cCR were randomly allocated to undergo surgery (arm A) or complete CRT up to the definitive radiation dose (arm B). The primary end point was 3-year disease-free survival (DFS). Finally, 71 patients were randomly assigned to the nCRT (n = 36) and dCRT (n = 35) arms. The median observation time was 35.7 months. The 3-year DFS rate was 56.43 % in arm A versus 54.73 % in arm B (hazard ratio [HR] = 0.862, 95 % confidence interval [CI] = 0.452 to 1.645, P = 0.652). The 3-year overall survival (OS) rates in arms A and B were 69.5 % and 62.3 % (HR = 0.824, 95 % CI = 403–1.688, P = 0.597), respectively. According to our treatment response evaluation criteria, survival of the patients with cCR after nCRT was not significant different between nCRT group and dCRT group. An optimized response evaluation strategy soon after nCRT may guide next therapy decisions for patients with locally advanced ESCC. [ABSTRACT FROM AUTHOR]

Background: The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options.Methods: We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed.Results: A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS.Conclusion: We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate whether standard uptake values (SUVs) of pretreatment 18F-FDG PET/CT were the surrogate parameters for predicting the outcomes in locally advanced esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. Materials and Methods: Sixty patients with esophageal squamous cell carcinoma underwent pretreatment 18F-FDG PET/CT and received definitive chemoradiotherapy. 18F-FDG metabolic parameters including SUVmax, SUVmean, SULpeak, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) of primary tumor were calculated. The receiver-operating characteristic (ROC) curve was used to determine the optimal cutoff value of FDG PET/CT-derived parameters that associated with treatment response. Estimating progression-free survival (PFS) and overall survival (OS) was analyzed by using Kaplan–Meier methods. Univariate and multivariate analysis for PFS and OS was performed using Cox regression. Results: Complete response was achieved in 38.3%. The 4-year OS and PFS rates were 48.6% and 44.4%, respectively. SUVmean with a cutoff value of 6.1 could predict complete response with sensitivity of 69.6%, specificity of 78.4%, and accuracy of 75%. Cox multi-factor regression analyses revealed SUVmean > 6.1 as an independent prognostic factor for OS (HR = 6.74, p = 0.02) and PFS (HR = 6.53, p < 0.001). Conclusions: Our study suggests that SUVmean of the primary tumor in pretreatment 18F-FDG PET/CT may be used as an independent predictor in esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired postsurgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC. Methods: JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients' data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model. Results: Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41–75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32–3.81] and many LVLs (HR 2.88, 95% CI 1.27–6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs. Conclusion: The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning. [ABSTRACT FROM AUTHOR]

Abstract Definitive chemoradiotherapy (dCRT) for the esophageal squamous cell carcinoma (ESCC) is performed for patients with cT4 disease without distant metastasis and also for those with cStage I‐III who are unable to tolerate or who refuse surgery. The rates of clinical complete response (cCR) after dCRT differ depending on the cStage, and patients who once achieved cCR frequently experience tumor recurrence. For those with residual tumor or with recurrence, salvage treatment is performed to achieve a cure. Several procedures have been reported as salvage treatments. Salvage esophagectomy is associated with high rates of morbidity and mortality, but can offer long‐term survival. With R0 resection, with cCR to dCRT, pulmonary complications appear to be important prognostic factors affecting overall survival (OS). Lymphadenectomy is performed for the patients with lymph node metastasis without recurrence of primary lesions or distant metastasis, but the contribution to long‐term OS is unclear. Metastasectomy is performed when distant metastasis is limited to the lung and there are few lesions, possibly contributing to long‐term OS. Endoscopic resection and photodynamic therapy are indicated for cT1a and cT1‐2 residual or recurrent tumors, respectively, and can yield favorable outcomes. Re‐CRT and re‐radiotherapy are performed for the patients with contraindications for surgery, but neither appears to contribute to long‐term OS despite high incidences of esophageal fistula and perforation.

ObjectiveNo study has reported the risk stratification of BMI and PNI in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (dCRT). This study aimed to construct a risk stratification to guide the treatment of ESCC following dCRT.MethodsA total of 1,068 patients with locally advanced ESCC who received dCRT were retrospectively analyzed. The impacts of clinicopathological factors on overall survival (OS) and progression-free survival (PFS) were analyzed. Besides, the novel prognostic indices of pre-therapeutic nutritional index (PTNI) and prognostic index (PI) were developed.ResultsThe median follow-up period of OS and PFS were 22.9 and 17.4 months, respectively. The high body mass index (BMI) group had better 5-year OS and PFS (36.4 and 34.0%) than the low BMI group (18.8 and 17.2%). The high prognostic nutritional index (PNI) group also had better 5-year OS and PFS (33.4 and 30.9%) than the low PNI group (17.5 and 17.2%). Multivariate Cox regression analysis showed that BMI and PNI were independent prognostic factors for OS and PFS. Based on nutritional indices, patients were categorized into the low-risk (PTNI = 1), medium-risk (PTNI = 2), and high-risk (PTNI = 3) groups with 5-year OS rates of 38.5, 18.9, 17.5%, respectively (p < 0.001) and 5-year PFS rates of 35.8, 17.6, 16.8%, respectively (p < 0.001). Besides, we also constructed a prognostic index (PI) for OS and PFS which was calculated based on statistically significant factors for predicting OS and PFS. The results revealed that the high-risk group had worse OS and PFS than the low-risk group (p < 0.001). Finally, RCS analysis demonstrated a non-linear relationship between the PNI, BMI, and survival for patients with ESCC. The death hazard of PNI and BMI sharply decreased to 41.8 and 19.7.ConclusionThe decreased pre-therapeutic BMI and PNI levels were associated with a worse survival outcome. BMI and PNI are readily available and can be used to stratify risk factors for locally advanced ESCC patients undergoing dCRT. The novel risk stratification may help to evaluate patients’ pre-therapeutic status and guide dCRT for locally advanced ESCC patients.

Objective: We aimed to construct risk stratification to help set individualized treatment strategies and intensities for different subgroups of patients. Methods: The Esophagus Immune Prognostic Index (EIPI) scores were constructed according to the levels of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) before treatment, and the patients were divided into low-, medium-, and high-risk groups. Finally, restricted cubic splines (RCS) were used to explore the relationship between dNLR, LDH, and survival outcomes. Results: The median follow-up period of overall survival (OS) and progression-free survival (PFS) were 25.2 and 17.6 months, respectively. Multivariate Cox regression analysis showed dNLR were the independent prognostic factors that were associated with OS and PFS. The 3-year OS and PFS rates in the low-, medium-, and high-risk groups were 44.4% and 38.2%, 26.1% and 23.6%, and 10.5% and 5.3%, respectively. Patients who received chemotherapy had better OS and PFS than those who did not receive chemotherapy in low-risk and medium/high-risk groups (all p

BackgroundThe globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.MethodsThis is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04460352.

Abstract Background Definitive chemoradiotherapy (dCRT) is the first choice treatment for patients with locally advanced non-small cell lung cancer (NSCLC), but up to 35% of dCRT-treated tumors may have persistent or recurrent disease. Since the last decades, multimodality therapy showing potential for cure has become the mainstream for treatment of locally advanced NSCLCs, even some that were initially inoperable. Although salvage lung resection after dCRT has been reported with acceptable survivals, experiences in this respect are still limited. Other concerns remain debatable and inconclusive, such as dosage of radiation exposure, long interval between dCRT and surgery, and surgical comorbidity. Case presentation A 73-year-old male former smoker with diagnosis of right lower lobe of lung squamous cell carcinoma (SqCC) with multiple mediastinal lymphadenopathy, cT4N2M0, stage IIIB, received salvage right lower lobe + right middle lobe bilobectomy through video-assisted thoracoscopic surgery (VATS) after dCRT and adjuvant CRT to a total of 9000 cGy dosage of radiation. The interval from the 1st and 2nd ends of radiation to the salvage surgery was 980 and 164 days, respectively. The pre-operative forced expiratory volume in the first second was 2.33 L (101% predicted) and the diffusing capacity of the lungs for carbon monoxide was 56% predicted. The operating time was 6.5 h, and the total estimated blood loss was 50 ml. The patient was discharged on the 7th postoperative day without major complications or bronchopleural fistulas. The patient was still alive 42 months after the initial diagnosis of advanced N2 lung SqCC, and kept progression-free for 7 months after salvage lung resection. Conclusions Salvage lung resection performed long after high-dose radiation therapy of dCRT is technically feasible through VATS approach in a patient with initially inoperable cT4N2M0 stage IIIB NSCLC, and can be an alternative consolidative treatment for locally advanced NSCLC.

Pancreas is an organ that is hardly affected by metastasis from other primary cancers; also, pancreatic metastasis from esophageal squamous cell carcinoma (ESCC) is an extremely infrequent entity. Metastatic esophageal cancer has a poor prognosis and the five-year survival rate is less than 5%. Here, we described a rare case of a 78-year-old woman presented with abdominal bloating, intermittent mild nausea, and loss of appetite and weight. Esophagogastroduodenoscopy revealed ESCC in the upper part of esophagus. A mass lesion between the head and body of pancreas was detected during metastatic work-up. Endoscopic ultrasound-guided fine needle aspiration was performed, morphologic features and immunohistochemistry confirmed metastatic squamous cell carcinoma from esophagus. Definitive chemoradiotherapy with curative intent was done on both oesophageal and pancreatic lesion. Interestingly, after nine months of treatment, the patient had no issues either in esophagus or in abdomen. In conclusion, local therapy could be considered as one of the best choices to improve the overall survival in ESCC with single metastasis to pancreas.

Purpose: This trial aims to explore the efficacy and safety of involved-field irradiation (IFI) combined with paclitaxel plus cisplatin as concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT).Methods: Enrolled patients with locally advanced ESCC were treated with definitive concurrent chemoradiotherapy. IFI was administered adopting IMRT and the total dose was 61.2 Gy delivered in 34 fractions. On the first day of radiotherapy, the patients were treated with paclitaxel and cisplatin one cycle per month for 2 cycles followed by the same regimen in consolidation chemotherapy for two cycles. The primary endpoint of the study was the 2-year locoregional recurrence-free survival (LRFS) rate, and secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety.Results: Between January 2018 and September 2020, 108 patients participated in the trial. 78.7% (85/108) of patients completed all 4 cycles of chemotherapy. The median follow-up of the surviving patients was 33.9 months (interquartile range, 29.2-41.1). The 2-year LRFS rate, as the primary endpoint, was 64.2%. In addition, the median PFS was 39.2 months, and 1-year and 3-year OS rates of 88.0% and 63.3%, respectively. Among the patients, out-of-field regional failure was seen in only 7 (6.5%) patients. Neutropenia grade 3 and 4 occurred in 21.3% and 37.0% of the patients, respectively.Conclusions: IFI using IMRT combined with paclitaxel and cisplatin concurrent chemotherapy for locally advanced ESCC yields encouraging local control and overall survival, but high hematological toxicity. Trial registration Clinical Trials ChiCTR1800017039. [ABSTRACT FROM AUTHOR]

Background: The optimal evidence-based management for the subsets of locally advanced esophageal squamous cell carcinoma (ESCC) patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities is currently lacking. This study aimed to assess the safety and local control rate (LCR) of S-1 (tegafur–gimeracil–oteracil potassium) combined with radiotherapy in these subsets of ESCC patients. Methods: Locally advanced ESCC patients who rejected or were intolerant to intravenous chemotherapy due to age >75 years or serious comorbidities were enrolled in a prospective, single-arm, phase 2 trial. The patients were treated with definitive concurrent chemoradiotherapy with S-1, which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end-point was the 3-year LCR. Results: One hundred five ESCC patients were recruited between March 2013 and October 2015. At the median follow-up of 73.1 months (IQR 65.5–81.4 months), 3-year LCR was 61.1%, and 1, 3, and 5-year overall survival was 77.9, 42.3, and 24.8% respectively. For safety analysis, ≥grade 3 acute adverse events included thrombocytopenia (6.7%), leukopenia (2.9%), anemia (1.0%), anorexia (1.0%), fatigue (10.5%), hiccup (1.0%), pneumonitis (4.8%), and esophagitis (3.8%). Two patients (1.9%) died of late esophageal hemorrhage, and one patient (1.0%) died of late radiation-induced pneumonitis. Conclusion: S-1 is a promising regimen in concurrent chemoradiotherapy with low toxicity and a favorable LCR in ESCC patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities. Clinical Trial Registration: ClinicalTrials.gov , NCT01831531. [ABSTRACT FROM AUTHOR]

Abstract As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p

Chen Wang,1,* Jiaqi Tong,2,* Mengqiu Tang,3 Yunyun Lu,3 Gaofeng Liang,4 Zhanchun Zhang,3 Tian Chen3 1Department of Gastroenterology, Ningbo Medical Center, Lihuili Hospital, Ningbo, People’s Republic of China; 2Department of Hematology, Ningbo Medical Center, Lihuili Hospital, Ningbo, People’s Republic of China; 3Department of Radiation Oncology, Ningbo Medical Center, Lihuili Hospital, Ningbo, People’s Republic of China; 4Department of Thoracic Surgery, Ningbo Medical Center, Lihuili Hospital, Ningbo, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian Chen Email lhldbyyct@126.comBackground: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed.Methods: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival.Results: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (> 2.07) and PLR (> 183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045).Conclusion: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.Keywords: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, esophageal squamous cell carcinoma, definitive chemoradiotherapy, surgery, prognostic factor, reference marker

BackgroundThe optimal evidence-based management for the subsets of locally advanced esophageal squamous cell carcinoma (ESCC) patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities is currently lacking. This study aimed to assess the safety and local control rate (LCR) of S-1 (tegafur–gimeracil–oteracil potassium) combined with radiotherapy in these subsets of ESCC patients.MethodsLocally advanced ESCC patients who rejected or were intolerant to intravenous chemotherapy due to age >75 years or serious comorbidities were enrolled in a prospective, single-arm, phase 2 trial. The patients were treated with definitive concurrent chemoradiotherapy with S-1, which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end-point was the 3-year LCR.ResultsOne hundred five ESCC patients were recruited between March 2013 and October 2015. At the median follow-up of 73.1 months (IQR 65.5–81.4 months), 3-year LCR was 61.1%, and 1, 3, and 5-year overall survival was 77.9, 42.3, and 24.8% respectively. For safety analysis, ≥grade 3 acute adverse events included thrombocytopenia (6.7%), leukopenia (2.9%), anemia (1.0%), anorexia (1.0%), fatigue (10.5%), hiccup (1.0%), pneumonitis (4.8%), and esophagitis (3.8%). Two patients (1.9%) died of late esophageal hemorrhage, and one patient (1.0%) died of late radiation-induced pneumonitis.ConclusionS-1 is a promising regimen in concurrent chemoradiotherapy with low toxicity and a favorable LCR in ESCC patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities.Clinical Trial RegistrationClinicalTrials.gov, NCT01831531.

Background: No post-treatment follow-up methods have been established yet for patients with esophageal carcinoma who undergo radical esophagectomy (Surg) or who show complete response to definitive chemoradiotherapy (dCRT-CR). The purpose of this study was to investigate the current status of follow-up of the Surg and dCRT-CR patients in Japan, and understand the current reality and problems to establish an optimal follow-up method. Methods: A questionnaire on the follow-up method adopted was sent by e-mail to 124 institutions approved by the Japan Esophageal Society as training institutions for board-certified esophageal surgeons; responses were received from 89 institutions. The data were compared with those obtained by a similar survey conducted in 2014. Results: Follow-up methods markedly varied among institutions. Almost all institutions scheduled computed tomography and upper gastrointestinal endoscopy at least once a year up to postoperative year 5 for both the Surg and dCRT-CR groups. At least 70% of the institutions continued follow-up up to postoperative year 10, and this proportion had increased as compared to that reported from the 2014 survey. Only 25–30% of the institutions scheduled follow-up screening for metachronous head and neck cancer for both groups, and the health-related quality of life (HR-QOL) after the treatment were seldom assessed. These trends remained unchanged as compared to those reported from the 2014 survey. Conclusions: The results suggest that the consensus of follow-up protocol could not be established. More attention is required for detection of metachronous cancers and assessment of the HR-QOL. Establishment of a consensus-based follow-up system and verification of its effectiveness are required. [ABSTRACT FROM AUTHOR]

Abstract Background Esophagectomy is still advised as an additional treatment for pathological T1b (pT1b) esophageal squamous cell carcinoma (ESCC) following attempted endoscopic resection (ER). ER followed with definitive chemoradiotherapy (dCRT) has shown increased quality of life as well as comparable oncological outcomes to esophagectomy. However, there is no well-designed phase III trial to compare the two treatments for patients with pT1b ESCC. Methods One hundred seventy-six patients with clinical stage N0 (cN0) and pT1b ESCC will be recruited at three centers and randomly assigned to the esophagectomy group or the dCRT group. The clinical lymph node status will be measured by image examination, including computer tomography and positron emission tomography–computed tomography. The pathological tumor status will be diagnosed after endoscopic submucosal dissection (ESD). All patients will be followed up for 60 months after randomization. The primary endpoint is 5-year overall survival. The secondary endpoints are quality of life, related adverse events, 3-year overall survival, and relapse-free survival rates. Discussion To the best of our knowledge, this is the first phase III randomized controlled trial to compare esophagectomy and dCRT for patients with cN0-pT1b ESCC after ESD. Based on the results of this study, we will show whether dCRT will benefit patients more than esophagectomy, which will contribute more high-quality evidence to the primary salvage treatment for these patients. Trial registration ClinicalTrials.gov, NCT04135664 . Registered on Aug. 10, 2019.

Abstract Background Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC). Methods Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman’s rank correlation, Mann–Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan–Meier method, and Cox proportional hazards models. Results The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = − 0.547, p = 0.003) and TTP (r = − 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014). Conclusions The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.

Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses., Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m 2 of paclitaxel and 25 mg/m 2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170)., Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P <  0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P <  0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P  = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P  = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs ( P  = 0.036)., Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis., Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou., Competing Interests: All authors have no conflicts of interest to declare., (© 2024 The Author(s).)

Il s'agissait d'évaluer l'efficacité en termes d'échec ganglionnaire du curage ganglionnaire cervical initial dans les carcinomes épidermoïdes de l'oropharynx de stade N2-3 pris en charge par chimioradiothérapie exclusive, ainsi que l'impact dosimétrique et la tolérance aiguë et tardive de cette approche. Tous les patients consécutivement pris en charge entre 2009 et 2018 par chimioradiothérapie exclusive à l'aide d'une radiothérapie conformationelle avec modulation d'intensité (RCMI) pour un carcinome épidermoïde de l'oropharynx de stade N2-3 selon la septième édition de la classification TNM American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) ont été rétrospectivement inclus. La stratégie thérapeutique consistait en une chimiothérapie d'induction, suivie d'une chimioradiothérapie exclusive à base de cisplatine précédée ou non d'un curage ganglionnaire cervical. Le curage ganglionnaire cervical a été discuté au cas par cas en réunion de concertation multidisciplinaire dédiée chez les patients en situation de réponse dissociée à la chimiothérapie d'induction, à savoir une réponse de meilleure qualité sur la tumeur primitive que sur les ganglions. Une chimioradiothérapie sans curage ganglionnaire cervical a été systématiquement réalisée en cas de réponse ganglionnaire majeure à la chimiothérapie d'induction (diminution en taille de 90 % ou plus). La RCMI délivrait en boost intégré une dose de 70 Gy en 35 fractions dans les volumes tumoraux macroscopiques, 63 Gy dans les aires ganglionnaires à risque intermédiaire ou en rupture capsulaire et 54 Gy dans celles irradiées à visée prophylactique. Deux groupes ont été constitués : 47 (62,7 %) patients sans curage ganglionnaire cervical initial, et 28 (37,3 %) patients avec un curage ganglionnaire cervical avant la chimioradiothérapie. Les caractéristiques initiales des patients n'étaient pas statistiquement différentes entre les deux groupes. Le recul médian était de 60,1 [3,2–119] mois. L'incidence des échecs ganglionnaires était plus élevée chez les patients n'ayant pas eu de curage ganglionnaire cervical (p = 0,015). Le taux d'échec ganglionnaire à 5 ans était de 19,8 % (intervalle de confiance à 95 % : 7,4–30,6) en l'absence de curage ganglionnaire cervical contre aucune rechute (0 %) après curage ganglionnaire cervical. Tous les échecs ganglionnaires se trouvaient dans le volume cible prévisionnel à 70 Gy. Le curage ganglionnaire cervical a permis une diminution de la dose moyenne reçue par la parotide homolatérale (p = 0,01), la mandibule (p = 0,02) et la thyroïde (p = 0,02). La tolérance aiguë de la chimioradiothérapie avait tendance à être meilleure chez les patients ayant eu un curage ganglionnaire avec une réduction des événements indésirables de grade ≥ 3 (p = 0,04), de l'arrêt précoce de la chimiothérapie concomitante (p = 0,009) et du recours à une gastrostomie (p = 0,008) en analyse unifactorielle. Au cours du suivi, il n'existait aucune différence entre les deux groupes en termes de xérostomie, de dysgueusie, de dysphagie ou de dépendance à la gastrostomie en analyse unifactorielle. Le curage ganglionnaire cervical avant la chimioradiothérapie exclusive dans les carcinomes épidermoïdes de l'oropharynx de stade N2-3 était associé à un très bon taux de contrôle ganglionnaire sans morbidité supplémentaire à moyen et long termes. The purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach. All patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70 Gy in 35 fractions on macroscopic tumour volumes, 63 Gy on intermediate-risk levels or extra-nodal extension and 54 Gy on prophylactic lymph node areas. Two groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1 months (range: 3.2–119 months). Incidence of neck failure was higher in patients without neck dissection (P = 0.015). The neck failure rate at 5 years was 19.8% (95% confidence interval: 7.4–30.6%; P = 0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70 Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P = 0.01), mandible (P = 0.02), and thyroid gland (P = 0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade ≥ 3 adverse events (P = 0.04), early discontinuation of concomitant chemotherapy (P = 0.009) and feeding tube-dependence (P = 0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis. Neck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity. [ABSTRACT FROM AUTHOR]

• MEDLINE (Ovid), EMBASE, and Cochrane Central Register of Controlled Trials were searched from database initiation (1946 for MEDLINE, 1974 for EMBASE, and 1995 for Cochrane) up until May 2021. • Eight studies were included in this review. Patients receiving neoadjuvant chemoradiotherapy with esophagectomy had better overall survival – HR 0.55; 95% CI: 0.49–0.62. • Toxicity was similar, between the two treatments. • Given the paucity of data and lack of uniform reporting of endpoints, further studies should be conducted. There currently exists limited data comparing definitive chemoradiotherapy to neoadjuvant chemoradiotherapy with esophagectomy for patients with esophageal carcinoma. While we await more trials, we conducted a systematic review and meta-analysis of randomized controlled trials and observational studies with either propensity score matched or multivariable analyses, to provide a better understanding of the relative efficacy and effectiveness. MEDLINE (Ovid), EMBASE, and Cochrane Central Register of Controlled Trials were searched from database initiation (1946 for MEDLINE, 1974 for EMBASE, and 1995 for Cochrane) up until May 2021. Articles were included if they reported on overall survival or toxicity data. Summary hazard ratio (HR) and 95% confidence interval (CI) was calculated using a random-effects DerSimonian-Laird model. Eight studies with a total of 16,647 patients were included in this review. Patients receiving neoadjuvant chemoradiotherapy with esophagectomy had better overall survival – HR 0.55; 95% CI: 0.49–0.62. Toxicity was similar, between the two treatments. Patients with esophageal carcinoma receiving neoadjuvant chemoradiotherapy and esophagectomy have better survival than patients receiving definitive chemoradiotherapy. Given the paucity of data and lack of uniform reporting of endpoints, further studies should be conducted. [ABSTRACT FROM AUTHOR]