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To establish whether there are geographic differences in treatments and outcomes for patients with kidney cancer (KC) in England which could potentially be improved by the creation of national guidelines. A multidisciplinary group convened by the charity Kidney Cancer UK developed Quality Performance Indicators (QPIs) for the treatment of KC. Adherence to these QPIs was reported for all patients with a histological diagnosis of KC diagnosed in England between 2017 and 2018. Utilising data extracted from national datasets, logistic and linear probability models were used to estimate geographic variation in the delivery of surgery and systemic anti-cancer therapy at Cancer Alliance and NHS trust levels. Results were adjusted for a priori confounders, including age at diagnosis, area deprivation of residence, and Charlson Comorbidity Index. Differences in overall survival are reported. The cohort comprised 18,640 tumours in 18,421 patients. Of tumours diagnosed, median patient age was 68 (interquartile range 58–77) years and 63.4% were in males. When stratified by Cancer Alliance, the proportions of T1a/T1b/N0/M0 KC that had radical nephrectomy (RN), nephron sparing surgery or ablation ranged from 53.3% (95% CI [48.7, 57.8]) to 80.3% (95% CI [73.0, 86.0]). For stage T1b-3 cancers, the proportion that received RN ranged from 65.6% (95% CI [60.3, 70.5]) to 77.3% (95% CI [72.1, 81.7]). Patients with M0 (n = 12,365) and M1 KC (n = 3312) at diagnosis had 24-month survival of 87.5% and 25.1%, respectively. Of patients diagnosed with M1 KC, 50.3% received systemic anti-cancer therapy, ranging from 39.7% (95% CI [33.7, 46.1]) to 70.7% (95% CI [59.6, 79.8]) between Cancer Alliances. The six-month survival of these patients was 77.4% compared to 27.6% for those that did not receive SACT. These major geographical differences in surgical and systemic therapy practice have led to national guideline development. • Analysis of 18,421 patients with Kidney Cancer presenting in England 2017–18. • Marked variations between Cancer Alliances in rates of surgery for primary kidney cancer. • Systemic anti-cancer therapy improves outcomes in metastatic kidney cancer patients. • Significant variations between Cancer Alliances in systemic anti-cancer therapy use. • Low rates of clinical trial recruitment. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592–3864 AUD (£1350–2012 GBP) per patient was estimated had these patients been treated with the protocol. The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol. • Cost per 5-year local control outcome was similar for Stage I-III breast cancer ranging from $29,675 AUD to $32,478 AUD. • Cost per 5-year overall survival outcome was cheaper for stage III breast cancer compared with Stage I-II breast cancer. • Use of the FAST-Forward ultrahypofractionation protocol significantly reduces RT costs. [ABSTRACT FROM AUTHOR]

Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin–paclitaxel compared with placebo plus carboplatin–paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin–paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54 - 0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin–paclitaxel versus carboplatin–paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17 - 0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60 - 1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin–paclitaxel was consistent with the first interim analysis. Dostarlimab in combination with carboplatin–paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile. • RUBY compared dostarlimab + chemotherapy to chemotherapy alone in patients with primary advanced/recurrent EC. • RUBY showed statistically significant and clinically relevant improvements in OS with dostarlimab + chemotherapy. • These are clinically important results for patients with primary advanced/recurrent EC. • This represents a new standard of care for primary advanced/recurrent EC. [ABSTRACT FROM AUTHOR]

• Diaphragmatic stripping is associated with acceptable postoperative morbidity. • The procedure offers significant advantage on patients' survival. • The survival benefit seems to be independent of the stage at diagnosis or adequacy of tumor debulking. Diaphragmatic stripping is a standard procedure that is performed in a significant proportion of patients undergoing surgical cytoreduction for advanced ovarian cancer. The objective of the present study is to evaluate morbidity and survival outcomes among patients offered diaphragmatic surgery for primary diagnosed optimally resected ovarian cancer. We conducted a retrospective cohort study, identifying patients that were offered surgery between 2016 and 2021 for primary diagnosis of ovarian cancer. Cases that had diaphragmatic stripping or partial diaphragmatic resection were selected and compared to cases that did not require this procedure. Kaplan-Meier and Cox-regression analyses were applied to evaluate survival outcomes. Overall, 61 patients that had diaphragmatic stripping were identified. Severe postoperative complications (Clavien-Dindo 3 +) were noted in 19 patients (31 %). Survival analyses denoted that the stage of the disease at the time of diagnosis, as well as the timing of the surgical procedure (PDS vs IDS) and the completion of tumor debulking were factors that significantly affected the recurrence free and overall survival of patients. Severe postoperative morbidity was a significant predictor of the overall survival. Multivariate cox-regression analysis that was adjusted for the stage of the disease revealed that preoperative pleural effusion, optimal (compared to complete) tumor resection and the occurrence of postoperative complications significantly affected the overall survival of patients. Compared to patients that did not have diaphragmatic surgery, patients submitted to diaphragmatic stripping or resection had improved progression free and overall survival rates, irrespective of the stage of the disease at diagnosis or the adequacy of resection status. Diaphragmatic surgery is feasible in advanced ovarian cancer patients with acceptable morbidity that mainly refers to postoperative pleural effusion. Its positive impact on patients' survival requires further investigation. [ABSTRACT FROM AUTHOR]

Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients. • 5-year survival was 45% for soft tissue sarcoma patients and 66% for bone sarcoma patients. • The Aarhus composite biomarker score is a prognostic factor for soft tissue sarcoma. • A previous cancer diagnosis is negatively associated with overall survival in soft tissue sarcoma patients. [ABSTRACT FROM AUTHOR]

Long-term follow-up for the CLEAR trial confirms the deep and durable tumor-response benefit of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma (aRCC). The results support the use of this combination as a standard-of-care first-line treatment for aRCC. In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2–not estimable) for the CR group, 30.5 mo (95% CI 22.4–not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5–21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60–78%), intermediate-risk (73%, 95% CI 67–79%), and poor-risk (70%, 95% CI 54–85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861. [ABSTRACT FROM AUTHOR]

Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT). From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1–3: 57–92%) and 78% (q1–3: 60–85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0–1, 45% were employed at prior capacity and 28% were working with impairment. Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour. • IDH-mutant Grade 3 glioma are brain tumours with good prognosis. • Standard management consists of surgery, radiotherapy and temozolamide. • Large tumours pose challenge of achieving local control with acceptable morbidity. • PET imaging and modern radiotherapy techniques allow conformal tumour delineation. • These techniques allow for good long-term control, survival and function. [ABSTRACT FROM AUTHOR]

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• Chemotherapy response score is a valuable tool that helps determine patients at risk of earlier relapse and death. • The importance of debulking surgery remains significant even in those with minimal response to chemotherapy. • Survival differences of CRS 1-2 vs CRS 3 patients were similar to those of patients with platinum resistant vs sensitive disease. The chemotherapy response score (CRS) has been widely adopted as a predictive tool for ovarian cancer survival. In the present study, we seek to define differences in survival rates among patients grouped in the traditionally established three-tiered system and those who have not been offered debulking surgery. We designed a retrospective cohort study involving women treated with chemotherapy and offered interval or late debulking surgery for ovarian cancer. Twenty-eight women were not considered for a debulking procedure for various reasons. Of the 89 women who were finally offered interval debulking or late debulking surgery, 28 had a CRS 1 score, 34 had a CRS 2 score and 27 had a CRS 3 score. Significant differences were noted in the progression-free survival (PFS) and overall survival (OS) of patients based on the CRS stratification, although survival rates were considerably longer for all three groups compared to those of patients who were not offered surgery. Cox regression univariate analysis revealed that suboptimal debulking and CRS 1 or no surgery had a significant negative impact on PFS and OS rates. The binary stratification of CRS (CRS 1–2 vs CRS 3) revealed comparable differences in the PFS and OS to those in the groups that were stratified as platinum resistant and platinum sensitive. The chemotherapy response score is a significant determinant of ovarian cancer survival that helps evaluate the risk of early disease relapse and death and may soon be useful in guiding patient-tailored treatment. [ABSTRACT FROM AUTHOR]

• FDG-PET/CTs detects a higher rate on lymph node metastasis compared with conventional CT in ovarian cancer patients. • In the literature, CT positive lymph nodes show an inverse effect on complete resection rate, PFS and OS. • In our Cohort FDG-PET/CT positive lymph node show no correlation with intra- and perioperative outcomes or the OS. Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease. The potential significance of PET-positive supradiaphragmatic lymph nodes (SDLNs) for these parameters was evaluated. All patients with FIGO IIA-IVB EOC diagnosed between March 2014 and January 2021 at our certified gynaecological cancer centre, who underwent FDG PET/CT before primary surgery were retrospectively included. Fifty-three consecutive patients were included in the study. Eighteen (34 %) patients had PET-positive SDLNs. We could not demonstrate a significant correlation between PET-positive SDLNs and median overall survival (OS; SDLN-positive: 58.76 months, SDLN-negative: 60.76 months; p = 0.137) or intra- or perioperative outcomes. FDG PET/CT has a higher detection rate for SDLNs in patients with ovarian cancer than CT has, as described in the literature. Moreover, PET-positive SDLNs failed to predict intraoperative outcomes or overall survival. [ABSTRACT FROM AUTHOR]

The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence, who approved monotherapy alone in England and Wales. The aim of this study was to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma in the palliative setting in Scotland. We analysed the electronic records of patients who started pembrolizumab-containing treatment between 1 March 2020 and 30 September 2021. Outcomes included overall survival, progression-free survival (PFS), the duration of response and the disease control rate. Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to those in the KEYNOTE-048 study, although our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n = 76), 12- and 24-month overall survival were 45% and 27%, respectively. For patients receiving pembrolizumab–chemotherapy (n = 15), 12-month overall survival was 60% (24-month overall survival had not yet been reached). Experiencing one or more immune-related adverse event (irAE; versus no irAEs), of any grade, was associated with favourable overall survival and PFS for patients receiving monotherapy in both univariable Log-rank analysis (median overall survival 17.4 months versus 8.6 months, respectively, P = 0.0033; median PFS 10.9 months versus 3.0 months, respectively, P < 0.0001) and multivariable analysis (Cox proportional hazards regression: overall survival hazard ratio 0.31, P = 0.0009; PFS hazard ratio 0.17, P < 0.0001). Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show that irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing that irAEs are generally a positive marker of programmed death-ligand 1 (PD-L1) inhibitor response. • Pembrolizumab efficacy and toxicity were similar between our real-world and KEYNOTE-048 data. • Locally advanced, treatment-naïve patients had comparable outcomes to other groups. • irAEs were associated with better outcomes when receiving pembrolizumab. [ABSTRACT FROM AUTHOR]

The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P =.005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P =.65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P <.001). Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach. [ABSTRACT FROM AUTHOR]

The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40–50 Gy/20–25 fractions). SBRT dose was 30–40 ​Gy in 5 fractions for patients treated with SBRT alone and 25–32 ​Gy in 4–5 fractions for those treated with SBRT ​+ ​WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines. Median follow-up was 32 (range: 3.4–70.4) months. Imaging at median 2.2 (0.6–8.1) months post-SBRT showed median 43.2 ​% (range: 2–100 ​%) decrease in the largest diameter and median 68.7 ​% (range: 27.9–100 ​%) SUV reduction. There were 3 cases of local progression at 8.7–10.6 months. Estimated LC was 100 ​% at 6 months and 71.6 ​% at 12, 24 and 36 months. Estimated median OS was 100 ​% at 6 months, 76.9 ​% at 12 months, and 61.5 ​% at 24 and 36 months. Acute toxicity (n ​= ​13; 92.9 ​%) included grade (G)1 (n ​= ​8), G2 (n ​= ​4), and G4 (necrosis; n ​= ​1). Late toxicity included G2 edema (n ​= ​1) and G4 necrosis (n ​= ​2, including 1 consequential late effect). Only patients treated with SBRT ​+ ​WBRT experienced acute/late G4 toxicity, managed with resection or steroids. SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n ​= ​2) occurred in the SBRT ​+ ​WBRT group, it was successfully salvaged. [ABSTRACT FROM AUTHOR]

We present 7 years of clinical experience with single-agent pembrolizumab immune checkpoint inhibitor immunotherapy in non-small cell lung cancers (NSCLC) from four UK cancer centres. This multi-institutional retrospective cohort study included 226 metastatic NSCLC patients. Outcomes were number and severity of immune-related adverse events (irAEs), median progression-free survival (mPFS) and median overall survival (mOS). Within our cohort, 119/226 (53%) patients developed irAEs. Of these, 54/119 (45%) experienced irAEs affecting two or more organ systems. The most common irAEs were diarrhoea and rash. The development of an irAE was associated with better mOS (20.7 versus 8.0 months; P < 0.001) and mPFS (12.0 versus 3.9 months; P < 0.001). The development of grade 3/4 toxicities was associated with worse outcomes compared with the development of grade 1/2 toxicities (mOS 6.1 months versus 25.2 months, P < 0.01; mPFS 5.6 months versus 19.3 months, P = 0.01, respectively). Females had a higher proportion of reported grade 3/4 toxicities (13/44 [29.5%] versus 10/74 [13.5%], P = 0.03). Using a multiple Cox regression model, the presence of irAEs was associated with a better overall survival (hazard ratio = 0.42, 95% confidence interval 0.29–0.61; P < 0.01) and better PFS (hazard ratio 0.38, 95% confidence interval 0.27–0.53; P < 0.001). In this multicentre retrospective cohort study, the development of at least one irAE was associated with significantly longer mPFS and mOS; however, more severe grade 3 and 4 irAEs were associated with worse outcomes. Delayed-onset irAEs, after the 3-month timepoint, were associated with better clinical outcomes. • Multi-institution experience (n = 226) of pembrolizumab monotherapy in advanced lung cancer. • Development of immune-related adverse events (irAEs) associated with improved outcomes. • Onset of irAEs at >3 months from treatment start associated with better outcomes. • Patients with CTCAE grade 1–2 toxicity did better than those with grade 3–4 toxicity. [ABSTRACT FROM AUTHOR]

The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients. We systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. The combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50–0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate. Our meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration. • No evidence that doublet therapy is more effective than monotherapy in second-line treatment of biliary tract cancer. • FOLFOX demonstrated higher activity compared with active symptom control. • Two studies showed conflicting results assessing the activity of 5-FU/LV ± nal-IRI. • Our meta-analysis supports the role of nal-IRI in biliary tract cancer. [ABSTRACT FROM AUTHOR]

Patients with advanced cancer sometimes travel to locations that have the treatment that they need. We explored the prognostic factors of survival in patients with advanced lung cancer who travel long distances in Taiwan. We obtained data from the National Taiwan University Hospital (NTUH) Integrated Medical Database. Patients who received a diagnosis of stage IV lung cancer from 2010 to 2019 and were treated in NTUH and its Hsinchu and Yunlin branches were enrolled. Factors associated with survival were analyzed using a Cox hazard regression model. In total, 6178 patients with stage IV lung cancer were enrolled. Young age, female sex, smaller primary tumor size, better performance, and non-squamous cell non–small cell histology were independently associated with longer survival. Treatment in medical centers and long travel distances (>50 km) were associated with longer survival in the univariate analysis but not in the multivariate analysis (hazard ratio [HR]: 1.04, p = 0.361; HR: 0.99, p = 0.775, respectively). Participation in clinical trials was associated with longer survival in the univariate (HR: 0.53, p < 0.001) and multivariate analyses (HR: 0.62, p < 0.001). For the 1144 patients in the Hsinchu area, enrolment in clinical trials was an independent prognostic factor (HR: 0.72, p = 0.040), whereas treatment in medical centers was not (HR: 0.95, p = 0.635). Long travel distances and treatment in medical centers were not independently associated with survival for patients with advanced lung cancer. Enrolment in clinical trials was an independent prognostic factor. [ABSTRACT FROM AUTHOR]

The aim of this systematic review with meta-analysis was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). We searched PubMed, Embase and Cochrane Library until 1 July 2022 for mCRPC trials testing PD-1/PD-L1 checkpoint inhibitors. We measured the efficacy and safety using overall survival, progression-free survival (PFS), overall response rates (ORR), prostate-specific antigen (PSA) response rate or treatment-related adverse events (TRAEs). When possible, data were meta-analysed. Thirteen studies involving 2533 participants were included in this meta-analysis. The pooled hazard ratio for overall survival was 0.81 (95% confidence interval 0.42–1.20, I2 = 80.3%, P Heterogeneity ＜0.001) and for PFS was 0.65 (95% confidence interval 0.38–0.92, I2 = 72.2%, P Heterogeneity = 0.013). Furthermore, better ORR (relative risk = 2.77, 95% confidence interval 1.25–6.13, I2 = 0%, P Heterogeneity = 0.699) was found in PD-L1-expressing tumours. However, no statistical trends between PD-L1 status on PSA response rate (relative risk = 0.79, 95% confidence interval 0.5–1.25, I2 = 0%, P Heterogeneity = 0.953) and tumour mutational burden on ORR (relative risk = 2.53, 95% confidence interval 0.49–13.12, I2 = 74.5%, P Heterogeneity = 0.02) were observed. The pooled proportions of TRAEs and ≥ grade 3 TRAEs were 85.1% (95% confidence interval = 71.7–98.5%) and 31.6% (95% confidence interval = 18.9–44.4%), respectively. This meta-analysis showed that among selected populations of men with mCRPC, anti-PD-1/PD-L1 combination treatment may significantly increase the PFS benefits. However, overall survival in mCRPC warrants further testing. • Efficacy and safety of PD-1/PD-L1 inhibitors in mCRPC patients was evaluated. • Thirteen studies involving 2533 participants were included in the meta-analysis. • Anti-PD-1/PD-L1 treatment may significantly increase the PFS benefits. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of –3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3–13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80–1.53; P = 0.54). Oncological outcomes are awaited. Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure – overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway. • Oral oestrogens (E2) in men have previously been investigated as a treatment for prostate cancer but were limited by cardiovascular side-effects. • Transdermal application (tE2) avoids these challenges. • The tE2 programme investigates this as androgen deprivation in men with prostate cancer. • Potential benefits include long-term bone health, metabolic profile and quality of life. • Recruitment is complete and efficacy data are expected from 2024 onwards. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is known to be a risk factor for postoperative infectious complications (PICs). However, the significance of postoperative hyperglycemia in non-DM cases has not been well investigated. We sought to establish whether postoperative hyperglycemia is associated with PICs and survival among patients with esophageal cancer, with a focus on non-DM cases. Methods: A total of 430 patients who underwent subtotal esophagectomy for esophageal cancer between 2014 and 2018 were enrolled. Postoperative blood glucose was measured by arterial blood gas test every 8 h from postoperative day (POD) 1 to POD4. The association between hyperglycemia (mean ≥ 200 mg/dl) and PICs or long-term outcomes on each POD was investigated. Results: There were 53 DM and 377 non-DM cases. PICs occurred in 127 patients. In the multivariate analysis of all cases, PICs were associated with hyperglycemia on POD1 or -2 (odds ratio [OR] = 1.69, 95% CI, 1.05–2.73, P = 0.031 for POD1; OR = 2.55, 95% CI, 1.10–5.93, P = 0.029 for POD 2). Among non-DM cases, the association was more evident, and persisted until POD4 (OR = 1.94, 95% CI, 1.16–3.24, P = 0.012 for POD1; OR = 3.68, 95% CI, 1.28–10.6, P = 0.016 for POD2; OR = 3.07, 95% CI, 1.11–8.51, P = 0.031 for POD4). Survival analyses limited to R0 cases revealed hyperglycemia on POD2 as an independent prognostic factor in all cases (N = 412) [hazard ratio (HR) = 2.61, 95%CI, 1.21–5.63, P = 0.014], with the prognostic impact more evident among non-DM cases (N = 360) (HR = 4.38, 95% CI, 1.82–10.57, P = 0.0010). Conclusion: Postoperative hyperglycemia is associated with PICs and worse survival after esophagectomy, particularly in patients without DM. [ABSTRACT FROM AUTHOR]

The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan–Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4–93.4), 74.9% (95% confidence interval 66.1–81.7) and 57.2% (95% confidence interval 45.8–67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06–3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01–3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34–4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4–70.9), 31.5% (95% confidence interval 22.8–40.6) and 24.7% (95% confidence interval 16.0–34.3). This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome. • MDT is a promising treatment option for oligometastatic prostate cancer patients. • Three-dimensional total tumour volume and site of oligometastases are predictive factors of overall survival after MDT. • These findings may help to improve personalised treatment decisions for oligometastatic prostate cancer patients. [ABSTRACT FROM AUTHOR]

We aimed to investigate the impact of the worst pattern of invasion (WPOI-V), an indicator of biological aggressiveness, on survival outcomes, as well as the potential need for adjuvant radiotherapy in squamous cell oral cavity cancers. A total of 162 patients who underwent surgical procedures at our center between 2017 and 2023 were included in the study. The median age of the patients was 65 years (range, 18-91 years). Tumor locations encompassed the lip (n=60), tongue (n=49), gingiva and buccal mucosa (n=23), and other sites (n=30). Patients were categorized into two groups: those with early-stage disease (T1 -2 or N0) (n=80) and those with locally advanced disease (T3-4 or N+) (n=82). Cancer-specific survival (CSS) was defined as the time to local, regional, or systemic progression, while overall survival (OS) was defined as the time to death from any cause following the date of surgery. The Kaplan-Meier method was employed for survival analysis, and statistical significance was set at p<0.05. The median follow-up duration was 36 months, with a range from 0 to 72 months. Local, regional, and/or systemic progression was observed in 26 patients, resulting in distant metastasis in 13 cases, local regional relapse in 8 cases, and second primary lung cancer in 2 cases. The three-year Cancer-Specific Survival (CSS) was significantly worse in patients with the presence of WPOI-V (63% vs. 86.9%, p=0.000) (see Figure 1). The difference was notably more pronounced in early-stage or younger patients. In multivariate analysis, the only significant factor influencing CSS in the early stage was WPOI-V (p=0.008) (Figure 1).There was no significant difference observed in OS. [Display omitted] The presence of WPOI-V in both early-stage and locally advanced patients serves as an indicator of a poor prognosis. This finding may represent a novel factor that warrants consideration for the inclusion of adjuvant therapy in the treatment of early-stage patients. [ABSTRACT FROM AUTHOR]

The benefit of stereotactic body radiotherapy (SBRT) in metachronous oligometastatic breast cancer (OMBC) has previously been described and its use in current clinical practice is established. The role of SBRT in the management of synchronous OMBC remains uncertain. The aim of this study was to compare outcomes of SBRT-treated synchronous OMBC with those of SBRT-treated metachronous OMBC. This was a retrospective analysis of consecutive extracranial OMBC patients treated with SBRT at a single institution between 2011 and 2022. Kaplan–Meier methods were used to calculate progression-free survival (PFS), overall survival, local control and distant control. Log-rank tests were used to test any differences. Cox regression was used for univariate and multivariate analyses to identify predictive factors. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. In total, 74 OMBC patients with 113 lesions were analysed. The median follow-up was 20 months (range 0–98). Seventy per cent of patients presented metachronously and 30% synchronously. 30 Gy in three fractions was most commonly prescribed, resulting in a median biologically effective dose (BED at α/β = 10) of 60 Gy (range 35.7–112.5 Gy). Forty-nine per cent of patients switched systemic therapy post-SBRT (median time to switch: 14 months, range 0–79). Two patients (2%) experienced grade 3 acute toxicities with no grade ≥4 toxicities. At 2 years overall survival was 92.4% and PFS 39.0%, local control 85.9% and distant control 37.0%. For metachronous and synchronous disease, respectively, 2-year local control rates were 86.5% and 85.8% and PFS rates were 35.3% and 48.3%. The median PFS of metachronous and synchronous disease were 18 months and 17 months, respectively (P = 0.86). Predictive factors on multivariate analysis were treated site for overall survival, change in systemic therapy post-SBRT for PFS and BED for local control. Our data confirm SBRT as a well-tolerated treatment for OMBC with excellent local control rates regardless of metachronous or synchronous presentation. There is no suggestion that survival outcomes are inferior for synchronous disease. Further prospective studies are required to validate this finding. • SBRT is a well tolerated treatment for OMBC. • SBRT outcomes in synchronous OMBC are comparable with those of metachronous OMBC. • SBRT achieves excellent local control in synchronous and metachronous OMBC. [ABSTRACT FROM AUTHOR]

• The 13 genes (TMPRSS11E, TNNC2, HLF, FOXM1, PKMYT1, TCN1, RGS20, SYT8, CD1B, LY6K, MFSD4A, KLRG2 and APCDD1L) related with prognosis of NSCLC were identified. • The high-risk NSCLC patients had worse overall survival. • The immune cell infiltration and checkpoints were differential between the high-risk and low-risk NSCLC patients. Genomic instability (GI) is an effective prognostic marker of cancer. Thus, in this work, we aimed to explore the impact of GI derived signature on prognosis in non-small cell lung cancer (NSCLC) patients using bioinformatics methods. The data of NSCLC patients were collected from The Cancer Genome Atlas. Totally 1794 immune related genes were downloaded from immport database. The optimal prognosis related genes were identified by univariate and LASSO Cox analyses. The risk score model was built to predict the NSCLC patients' prognosis. The immune cell infiltration was analyzed in CIBERSORT. The 951 differentially expressed genes (DEGs) between the genomic stability (GS) and GI groups were enriched in 862 Gene ontology terms and 32 Kyoto Encyclopedia of Genes and Genomes pathways. Based on the 13 optimal genes, a prognostic risk score mode for NSCLC was established, and the high-risk patients exhibited worse overall survival. Moreover, the nomogram could reliably predict the clinical outcomes. The immune cell infiltration and checkpoints were significantly differential between the two groups (high-risk and low-risk). The GI related 13-gene signature (TMPRSS11E, TNNC2, HLF, FOXM1, PKMYT1, TCN1, RGS20, SYT8, CD1B, LY6K, MFSD4A, KLRG2 APCDD1L) could reliably predict the prognosis of NSCLC patients. [ABSTRACT FROM AUTHOR]

A paradigm shift in cancer treatment occurred with the advent of immune checkpoint inhibitors (ICI). ICI therapy has improved tumor response and increased overall survival in patients with solid tumors and hematologic malignancies. While ICI therapy has improved overall patient outcomes in oncology, it has also introduced novel adverse effects called immune-related adverse effects (irAEs). Studies have shown that the development of irAEs is associated with improved overall survival, but certain irAEs like pneumonitis and myocarditis are life threatening, and could result in death if not identified and treated early. Therefore, it is important for radiologists to be aware of complications arising from ICI administration, especially those related to the heart and lungs as they are associated with greater mortality. This paper will review the imaging features of cardiothoracic toxicities, recurrent and chronic irAEs, and atypical tumor responses associated with irAEs. • Imaging plays a key role in identifying the cardiothoracic complications of immunotherapy. • Some cardiothoracic complications are associated with high mortality and imaging plays a crucial role in their diagnosis. • Early detection of complications can prompt early initiation of treatment, allowing patients to continue immunotherapy. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care. All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests. In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Studies have shown that 25-hydroxyvitamin D (25(OH)D) is predictive of survival following a diagnosis of cancer. However, evidence of the relationship between 25(OH)D and the survival of patients with pancreatic cancer has been inconsistent. We hypothesized that circulating 25(OH)D concentrations may be positively correlated with better prognosis in advanced pancreatic cancer. PubMed, EMBASE, Cochrane Library, and Web of Science database entries through April 2023, along with the reference lists of related studies, were searched. Additionally, we extracted observational studies reporting the association between 25(OH)D concentrations and the outcome of interest (overall survival [OS]) in advanced pancreatic cancer patients aged 18 years or older. Ultimately, 7 articles involving 2369 patients were included in this systematic review and meta-analysis. The results indicated that 25(OH)D concentrations were positively correlated with OS (hazard ratio = 2.37; 95% confidence interval, 2.22–2.54; P <.001). No association was found between 25(OH)D and progression-free survival. There was significant heterogeneity between studies in terms of OS (I 2 = 85.5%, P <.001). Our subgroup analysis revealed that this high heterogeneity may be attributed to the studies' different regions, designs, sample sources, and detection methods of 25(OH)D. Additionally, Begg's and Egger's tests indicated the presence of publication bias. To our knowledge, this is the first meta-analysis to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer. Our results suggested that circulating 25(OH)D concentrations were positively correlated with OS, indicating that 25(OH)D may be a potential prognostic marker in advanced pancreatic cancer. This systematic review and meta-analysis was performed to evaluate the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and survival outcomes among patients with advanced pancreatic cancer. The results showed that 25(OH)D concentrations were positively correlated with overall survival among patients with pancreatic cancer, indicating that 25(OH)D concentration may be a potential prognostic marker in advanced pancreatic cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Concurrent chemoradiation therapy (CRT) followed by durvalumab had demonstrated significant survival benefit for unresectable stage III (USIII) non-small cell lung cancer (NSCLC) patients (pts) in PACIFIC trial. However, 20%-30% pts have no chance to receive immunotherapy due to disease progression (PD) or intolerable toxicity during CRT period. This prospective study aimed to evaluate safety and efficacy of concurrent durvalumab with CRT followed by durvalumab in USIII NSCLC. CRUISER is a multi-center phase 2 study with USIII NSCLC. All pts will receive concurrent durvalumab and CRT followed by durvalumab until PD or unacceptable toxicity. Optional induction therapy with one cycle is allowed upon investigators' decisions. The primary endpoint was the incidence of ≥3 grade immune-mediated adverse event (imAE). Second endpoints were progression free survival (PFS) according to RECIST 1.1, overall survival (OS), and objective response rate (ORR). Between Jan 2021 and Sep 2022, 35 pts from 4 hospitals were enrolled. Median age was 64 years, 85.7% were male, and 54.3% were squamous carcinoma. IIIA/ /IIIB /IIIC NSCLC accounted for 34.3% (12/35), 48.6% (17/35), and 17.1% (6/35), with most of them (91.4%, 32/35) having N2/N3 metastases. Among the 20 (57.1%) pts received induction therapy, 17 pts received durvalumab plus chemotherapy. The median total dose of radiotherapy was 60 Gy. As of December 8th, 2023, Grade ≥3 imAE occurred in 4(11.4%) of 35 pts. With median follow-up of 19.0 months (m), median PFS was 14.4m (95% CI 10.2, NE), and one-year PFS rate was 60.9%. A trend of better one-year PFS rate was observed in subsets with induction therapy than without (68.8% vs 50.5%), received ＞ one cycle concurrent chemoradiation than one cycle (64.3% vs 51.8%) and received durvalumab with ≥seven cycles than ＜seven cycles (82.3% vs 33.1%). Median OS was not reached, and one-year OS rate was 76.4%. ORR was 80% (20/25) in evaluable set. Concurrent durvalumab with CRT followed by durvalumab for USIII NSCLC is tolerable. Radiotherapy with induction therapy and more cycles of concurrent chemoradiation and durvalumab demonstrates better outcome via this treatment regimen. [ABSTRACT FROM AUTHOR]

Radiation esophagitis is frequent and annoying toxicity in high dose thoracic radiation therapy. Contralateral esophagus intensity modulated radiation therapy (CES-IMRT) has been proposed to mitigate this problem, and this is to report impact of CES-IMRT in definitive concurrent chemoradiotherapy (dCCRT) for lung cancer patients. 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 frequency and severity of esophagitis by pain-killer usage, analgesic quantification algorithm (AQA) score, and failure patterns in 159 CES-necessary patients. All patients underwent dCCRT (66 Gy in 30 fractions with concurrent chemotherapy). Actual CES-IMRT application was determined based on 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. 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. [ABSTRACT FROM AUTHOR]

The incidence of anal cancer and anal cancer death continues to rise. People of color (POC) have been underrepresented in prospective clinical trials, including trials that have established anal cancer treatment to include modern radiation therapy (RT) techniques and concurrent chemotherapy. We evaluated our institutional experience to determine if disparities in oncologic outcomes and treatment tolerability exist among POC. We performed a retrospective chart review of anal cancer patients who received definitive organ-preserving treatment for localized anal cancer between 2008 and 2020 at a single health system. Outcomes including overall survival (OS), local recurrence-free survival (LRFS), and progression free-survival (PFS) were estimated using the Kaplan-Meier method. Toxicities were scored using the National Cancer Institute-Common Terminology Criteria for Adverse Events v5. Of the 201 consecutively treated patients, 16% were stage I, 24% were stage II, and 58% were stage III. Mean age at diagnosis was 53 years (range 31 – 78 years). The majority (95%) were treated with intensity modulated RT technique and most (98%) patients received concurrent chemotherapy. Median RT dose was 54 Gy (range 45 to 60.2 Gy). Over half (n = 111) had human immunodeficiency virus infection (HIV) at time of cancer diagnosis; among those with HIV, 81% identified as POC. With a median follow-up of 4 years (range 0 – 14.8 years), POC with anal cancer (n = 127) had greater risk of dying than non-Hispanic White patients (n = 72), hazard ratio (HR) = 2.00, confidence interval (CI): 1.10-3.64, p = 0.02. POC were also more likely to have local recurrence compared to non-Hispanic White patients (HR = 2.67, CI 1.10-6.48, p = 0.03). No significant difference was observed with PFS (HR 1.54, CI 0.81-2.93, p = 0.185). Notably, HIV infection was not associated with differences in OS, LRFS, or PFS. The mean age of diagnosis was younger in POC at 50.7 years (standard deviation [SD] 10.4 years) compared to non-Hispanic White patients (58.1 years [SD 7.6 years]). POC were more likely to have prolonged RT course (> 5 missed RT sessions) compared to their non-Hispanic White counterparts, 30% vs 23%, respectively. While most acute and late toxicities were similar between the two groups, POC had higher likelihood of late grade 2 skin toxicities than non-Hispanic White patients, 17% vs 3%, respectively, p < 0.01. Our study found worse OS and LRFS among POC compared to non-Hispanic white patients. Sustained late skin toxicities and prolonged treatment times were more common among POC. HIV infection was not independently correlated with worse outcomes even though minority race and extended RT course were seen more frequently among the group with HIV infection. Addressing barriers and biases to diagnosis and treatment, as well as inclusion of POC in prospective clinical trials, are urgently needed to optimize treatment and close the disparity gap that POC with anal cancer may face. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is usually associated with a good prognosis. While tyrosine kinase inhibitors (TKIs) have shown significant improvement in overall outcomes for patients with iodine-refractory disease, locoregional failure does occur. Locoregional progression can be particularly challenging due to the proximity of the aerodigestive tract and can adversely affect quality of life and survival. Our study aims to assess the efficacy of stereotactic body radiotherapy (SBRT) for locoregional progressive disease in patients with thyroid cancer receiving TKIs. Between August 2016 and November 2023, 19 patients with non-anaplastic thyroid cancer were treated with SBRT and TKIs for locoregional progression. Demographics and treatment-related characteristics were collected. Treatment endpoints including local control (LC), progression-free survival (PFS), overall survival (OS), and toxicities were recorded. Patients with anaplastic histology, incomplete treatment, or without follow-up information were excluded. Of 19 patients meeting the criteria, 11 were female. The mean age of 71 years old. Fourteen lesions were differentiated papillary thyroid cancer, 4 dedifferentiated papillary thyroid, and 2 had other histologies. Eleven patients had disease within the thyroid bed, 5 with postoperative soft tissue neck recurrence, and 4 had cervical nodal metastases. SBRT median dose was 40 Gy (range 35- 50Gy) delivered in five biweekly fractions. Lenvatinib was the TKI in the majority of the cases (n = 14), followed by dabrafenib/trametinib (n = 4) and cabozantinib (n = 2). Planning target volume (PTV) average volume was 175 cc, V95 = 145cc, and D90 = 99%. No grade 3 or 4 toxicities were observed. 5 patients developed grade 2 dysphagia and 4 with fatigue. After a median follow-up of 23 months (range 7-63 months), four patients suffered local progression with an actuarial 12-month LC of 78 %- and 24-month LC of 62%. 12 and 24 months PFS and overall survival were 62.8%, 52.3%, 89.2%, and 82.3%, respectively. The use of SBRT in combination with TKIs in iodine-refractory patients appears to be safe and effective for locoregional relapse. Further studies are necessary to define the role of stereotactic body radiotherapy in the management of thyroid cancer. [ABSTRACT FROM AUTHOR]

Patients with locally advanced colon cancer (LACC) have a poor prognosis and face challenges in complete resection of the tumor. Currently, options for downstaging treatment for patients with unresectable LACC are limited, yet the conversion rate to resectable status is crucial for patient survival. This study aims to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) in patients with initially unresectable LACC. It is the largest single-center retrospective study to date. We included 181 patients diagnosed with initially unresectable LACC at a single institution between 2010 and 2023, who received NACRT. Unresectability was determined by multidisciplinary team discussion according to image examination or confirmed by exploratory laparotomy. Most patients received a daily irradiation (GTV 45-50 Gy/25F/5W) with XELOX regimen chemotherapy every 3 weeks for 4 cycles. Surgery scheduled 6–8 weeks after radiotherapy and adjuvant chemotherapy were given if patients converted to resectable LACC. Surgical conversion rates, R0 resection rates, and pathological complete response (pCR) rates were calculated to evaluate short-term efficacy. Overall survival (OS), progression-free survival (PFS), local control (LC), and disease-free survival (DFS) were calculated to evaluate long-term efficacy. Acute toxicities during NACRT and postoperative complications were assessed to evaluate treatment safety. Of the patients, 155 (85.6%) underwent surgical resection of the primary tumor after receiving NACRT, with 147 (81.2%) achieving R0 resection and 29 (16.0%) achieving pCR. Twenty-six patients (14.4%) underwent exploratory laparotomy or abandoned surgery. 81.5% (57/70) of patients initially diagnosed with bladder invasion avoided radical cystectomy. The median follow-up time was 71.6 months. The 5-year OS, 5-year PFS, and 5-year LC for the whole group were 74.4%, 64.4%, and 87.9%, respectively. The 5-year DFS after R0 resection was 73.8%. The 5-year OS for patients with R0 resection was significantly higher than for those who did not achieve R0 resection (83.8% vs 31.1%, p<.001), while there were no significant survival differences between patients with left-sided versus right-sided colon cancer or between pMMR/dMMR status. During NACRT, the incidences of grade 3-4 myelosuppression, mucositis/dermatitis, and gastrointestinal toxicity were 19.3%, 2.2%, and 6.1%, respectively. Three patients experienced anastomotic leakage after surgery. NACRT followed by radical surgery is safe and feasible for patients with initially unresectable LACC. NACRT as a conversion therapy achieves a high rate of tumor downstaging, R0 resection and long-term survival with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The object of this systematic review and meta-analysis is to assess the efficacy of addition of local therapy to systemic treatments in patients with advanced EC. A systematic literature search was conducted in PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer (EGJC) with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random-effect model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests. A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR 0.52, 95% CI 0.37–0.73, p < 0.001) and OS (HR 0.69, 95% CI 0.58–0.81, p < 0.0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment had significant survival advantage in both patients with oligometastasis (PFS: HR 0.45, 95% CI 0.31–0.64, p < 0.0001); OS: HR 0.62, 95% CI 0.48–0.79, p < 0.0001) and recurrence (OS: HR 0.55, 95% CI 0.37–0.81, p = 0.002). In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced esophageal cancer, particularly in those with oligometastasis or recurrent diseases. [ABSTRACT FROM AUTHOR]

Role of SBRT in patients who do not respond to NACT is not yet well defined. We conducted this study to evaluate the impact of SBRT in borderline resectable pancreatic cancer patients with suboptimal response to NACT All consecutive patients staged as BRPC at our center from 2016 to 2020 were included. All received NACT with mFOLFIRINOX or NAB-PACLITAXEL (4-6 cycles) followed by surgical assessment. Patients with radiological partial response (PR) were surgically explored, those with poor response or stable disease not amenable to R0 resection received SBRT and additional chemotherapy followed by surgical assessment. SBRT consisted of 42 -45 Gy over 5 fractions in 10 days. A total of 151 patients with BRPC were registered. During NACT, 44(29%) patients either defaulted or progressed and 107 (69.9%) patients completed at least 4 cycles of NACT and response assessment CECT scan was done. Post NACT, 36(33.6%) patients with partial response were surgically explored, 22(73%) underwent R0 and 8 (24%) had R1 resection (Group 1, n = 30). Remaining 71(66.3%) patients had suboptimal response to NACT and were not feasible for R0 resection received additional SBRT and CT. Post SBRT 28(26.1%) patients were surgically explored and 17 (77%) underwent R0 resection whereas 5 (23%) had R1 resection (Group 2, n = 22). Remaining 43(40%) (Group 3, n = 43) patients continued to receive palliative chemotherapy. At median follow up of 18 months, Median overall survival (OS) and 2-year OS for the whole group (107 patients) was 18 (13-22) months and 37.1% respectively. Group 1 (Patients undergoing curative resection after NACT) had median OS of 26 (19-32) months and 2-year OS of 56 % while Group 2 (patients with addition of SBRT after NACT to achieve curative resection) had median OS of 21 (13-28) months and 2-year OS was 40.9 %. (p value = 0.572). Median OS for the patients in non-resected group (Group 3, n = 43) was 13 months and 2-year OS was 25.6%. There was no significant difference in DFS of the R0 resection patients in Group 1vs 2. (p value = 0.250). Median OS and 2-year OS of the patients who had R0 resection was significantly better than the patients who had R1 resection (27 vs 18 months, 55.9% versus 30.8% respectively, p value = 0.046). There was no difference in surgical complications or postoperative mortality between the two groups. Only 1 patient had grade 2 and 1 patient had grade 3 RT related late GI toxicity. 7 (23%) in Group 1 and 8 (36%) patients had Surgical morbidity. Patients diagnosed with BRPC with suboptimal response to NACT precluding resection, benefit from addition of SBRT by increasing the resectability rate and outcomes similar to the patients having partial or good response to NACT alone. SBRT does not lead to additional surgical or RT related late toxicity. [ABSTRACT FROM AUTHOR]

The 5-year results of the FAST-Forward trial demonstrate non-inferiority of 26 Gy delivered in 5 daily fractions (fx) compared to 40 Gy in 15 fx for breast cancer patients receiving adjuvant radiotherapy (RT). In this trial, patients with an indication for cavity boost received either 10 Gy in 5 daily fx or 16 Gy in 8 fx. We employed a novel boost regimen of 5.2 Gy in one fx for greater consistency with the overall treatment paradigm. We hypothesize that this boost regimen is feasible with high rates of disease control and limited toxicity. Patients with non-metastatic invasive carcinoma or DCIS of the breast treated at our institution between 07/01/2019 and 6/1/2022 with adjuvant whole breast RT to 26 Gy in 5 daily fx with or without a single fx cavity boost were identified. Patient and tumor characteristics, treatment details, adverse events (AEs) and disease control outcomes were collected. Locoregional recurrence free survival (LR-RFS), regional recurrence free survival (RRFS), distant recurrence free survival (DRFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Correlations between toxicities and patient, tumor, and treatment characteristics were assessed using logistic regression. A total of 284 patients were included in the analysis with a median age of 72 (range = 39-95) and a median follow-up of 22 months (range = 0-46). 167 patients (59%) received a boost. Acute grade (G) ≥ 2 AEs, defined as those occurring ≤90 days after RT completion, developed in 25 patients (8.9%), with 8 patients (2.9%) experiencing an acute G3 AE. Late ≥G2 AEs developed in 15 patients (5.6%), with 7 patients (2.6%) experiencing a late G3 AE (G2: breast pain, n = 1; breast lymphedema, n = 4; arm lymphedema, n = 1; fibrosis, n = 3. G3: chest wall discomfort, n = 1; fibrosis, n = 6). Greater BMI (P = 0.015), breast volume (P = 0.002), cavity volume (P = 0.041) and bolus use (P = 0.048) were associated with an increased risk of ≥G1 acute AEs, and breast volume (P = 0.017) and bolus (P = 0.001) with ≥G2 acute AEs. Greater breast volume was associated with ≥G1 late AEs (P = 0.029) and was borderline for late ≥G2 AEs (P = 0.05). Receipt of a boost was not associated with higher toxicity risk. The estimated 24-month LR-RFS, RRFS, DRFS, and OS were 96%, 97%, 96%, and 97%, respectively. A 5-fraction ultra-hypofractionated regimen for patients receiving adjuvant whole breast RT for early-stage breast cancer results in excellent early disease control and acceptable rates of acute and late toxicities. Receipt of an ultra-hypofractionated boost of 5.2 Gy in one fx did not appear to increase risk of toxicity. This regimen may be appropriate for carefully selected patients, such as those of advanced age or with logistical challenges, and continued follow-up will be of value to characterize long-term effects of this regimen. Additional data on patient-reported acute and long-term outcomes will be collected and analyzed by the time of presentation. [ABSTRACT FROM AUTHOR]

Radiotherapy for CCA remains an area of research. ABC-07 [ISRCTN: 10639376] is a randomized trial (1:2 randomization) for newly diagnosed, inoperable, locally advanced CCA (n = 69), comparing 8 cycles of Gemcitabine/Cisplatin (GC) vs 6 cycles GC plus SBRT to the tumor (50 Gy in 5 fractions (Fr)). The primary endpoint of improving progression free survival was not met. Here, we examine the influence of BED, alongside patient and cancer variables, on disease outcomes. 45 patients were randomized to SBRT, of which 41 received SBRT. The protocol specified longer fractionation (67.5 Gy in 15 Fr) for larger tumors (>6cm, max 12cm) or inclusion of nodal disease. Reduced dose thresholds (45 Gy then 40 Gy in 5 Fr; 58.1 Gy then 45 Gy in 15 Fr) were specified to meet mean liver dose constraints. PTV D95% values (min dose (Gy) to 95% of planning target volume (PTV)) were extracted from DICOM plans and converted to BED (α/β = 10Gy) (termed PTV_D95%BED). Other predictor variables included were: age, performance status (PS), female sex, biliary stent in-situ, T-stage (3-4 vs 1-2), N-stage (1 vs 0), distal CCA (dCCA), PTV Volume (PTV_vol). PTV D95% association with overall survival (OS), progression free survival (PFS) and time to local progression (TLP) was initially tested by univariate Cox and visualized by Kaplan-Meier. Multivariate Cox models were fitted for each endpoint, fitting PTV_D95%BED and other predictor variables, using backward stepwise selection using p<0.2. For TLP, as all variables removed, p<0.3 was used instead. PTV volumes were median 65cc (range 21.5 – 498cc). PTV_D95%BED doses were median 72 Gy (IQR 57 – 100 Gy BED). Planned fractionation was 5 Fr (n = 30) or 15 Fr (n = 11). PTV volume vs PTV_D95%BED showed no correlation = -0.0003. By univariate Cox, PTV_D95%BED did not meet p<0.05 threshold against OS (HR 0.989, P = 0.36), PFS (HR 0.982, P = 0.068) or TLP (HR 0.980, P = 0.26). Multivariate model selected variables were: OS model: PS (HR 0.3, p 0.02), N-stage (HR 2.1, p 0.13), PTV_vol (HR 0.98, p 0.037); PFS model: D95%BED (HR 0.98, p 0.047), age (HR 0.96, p 0.054), PTV_vol (HR 0.997, p 0.17); Local progression model: D95%BED (HR 0.96, p 0.14), age (HR 0.94, p 0.18), dCCA (HR 0.27, p 0.25), T-stage3/4 (HR 2.5, p 0.24), PTV_vol (HR 0.995, p 0.21). We believe this phase II prospectively collected trial data shows a signal of dose effect in subsequent CCA outcomes. There appears to be no correlation with patient or cancer related variables. Models for prediction of tumor coverage should be incorporated into treatment pathway diagnostics; enabling selection of best candidates for SBRT. Better understanding of tumor biology would also aid in selecting patients where local control is more critical (i.e. lower metastatic propensity). [ABSTRACT FROM AUTHOR]

Indications for surgical treatment of metastatic spine tumors include neural decompression and fixation for restoration of spinal stability. Due to the frail nature of spinal oncology patients, the use of percutaneous techniques have become more widespread in addition to traditional open decompression. Percutaneous fixation combined with 'mini-open' decompression can allow for both stabilization and decompression through smaller, relatively muscle sparing approaches. These allows for smaller incisions and the potential for less surgical pain, faster recovery, and reduction of wound healing issues. All spinal fixation procedures performed between 2018 and 2022 for the treatment of metastatic spine tumors at a single institution was retrospectively reviewed. Patient demographics, primary malignancy, performance (ECOG) and spinal instability neoplastic scores (SINS) were collected, as well as trending of pain scores and overall survival. The decision of whether to use open or percutaneous fixation techniques may be influenced by the degree of instability, the amount of epidural disease and extent of decompression needed, as well as performance status and medical morbidities, and the patient's ability to tolerate an open procedure. We wish to compare patients that have undergone open or percutaneous spinal fixation techniques for the treatment of metastatic spine tumors to compare indications and outcomes. Retrospective study. All patients undergoing spinal fixation procedures for metastatic spine tumors between 2018 and 2022 at a single institution. Patient demographics, primary malignancy, performance score (ECOG), spinal instability neoplastic score (SINS), pain score, overall survival. All spinal fixation procedures performed between 2018 and 2022 for the treatment of metastatic spine tumors at a single institution was retrospectively reviewed. Patient demographics, primary malignancy, performance (ECOG) and spinal instability neoplastic scores (SINS) were collected, as well as trending of pain scores and overall survival. In our cohort, there were 156 open fixation procedures and 67 percutaneous procedures performed. The most common source of primary malignancy was lung (21.5%), followed by breast (16.1%), and hematological malignancy (15.2%). Poor overall survival was associated with head and neck malignancies (HR 7.25 CI 95% 3.09-17.01 p<0.001) followed by genitourinary (HR 2.66 95% CI 1.35-5.24 p=0.005). As expected, patients with a poorer presurgical ECOG score (3-4) demonstrated worse overall survival (HR 2.06 95% CI 1.12-3.80 p=0.020). When comparing open and percutaneous fixation procedures, there was no statistically significant difference in overall survival of open versus percutaneous techniques (HR 1.09 95% CI 0.77-1.56 p=0.620). Average initial ECOG scores of open vs percutaneous (1.481 vs 1.5) as well as SINS scores (11.77 vs 11.9) were similar indicating that both procedures were applied equally based on initial performance and stability scores. In a single institution review, we found that open and percutaneous fixation techniques were overall applied equally in terms of spinal instability and initial performance score, and did not demonstrate a difference in overall survival. Further analysis is necessary to understand additional details that lead to the indication for each type of technique in the treatment of spinal metastasis. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure. • First PARPi trial to show clinically meaningful OS benefit in HRD+ (BRCA/non-BRCA) newly diagnosed advanced ovarian cancer. • 5-Year OS rate in HRD+ disease was 66% with olaparib + bevacizumab versus 48% with placebo + bevacizumab. • Forty-six percent of HRD+ patients receiving olaparib + bevacizumab were progression free at 5 years, versus 19% on bevacizumab alone. • No new safety signals were observed, and the incidence of myelodysplastic syndrome/acute myeloid leukemia remained low. • Maintenance olaparib + bevacizumab as a standard of care may enhance potential for cure for HRD+ disease in this setting. [ABSTRACT FROM AUTHOR]

To investigate the survival outcomes, patterns and risks of recurrence in cN3c breast cancer patients after multimodality therapy, as well as the predictors of candidates for ipsilateral supraclavicular (SCV) area boosting. Consecutive cN3c breast cancer patients from January 2009 to December 2020 were retrospectively reviewed. Based on nodal response to primary systemic therapy (PST), patients were categorized into three groups: clinical complete response (cCR) not achieved in SCV lymph nodal (SCLN, Group A), SCLN cCR but axillary node (ALN) did not achieve pathological complete response (pCR, Group B), cCR in SCLN and pCR in ALN (Group C). The median follow-up time was 32.7 months. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64.6% and 43.7% respectively. Multivariate analysis showed cumulative SCV dose and ypT stage, ALN response and SCV response to PST were significantly associated with OS and RFS respectively. Compared with Group A or B, Group C showed significantly improved 3 y-RFS (53.8% vs 73.6% vs 100%, p = 0.003), and the lowest rate of DM as first failure (37.9% vs 23.5% vs 0%, p = 0.010). In Group A, the 3 y-OS for patients receiving the cumulative SCV dose of ≥60 Gy versus <60 Gy was 78.0% versus 57.3% (p = 0.029). Nodal response to PST is an independent prognostic factor for survival and pattern of failure. A cumulative SCV dose of ≥60 Gy is positively associated with improved OS, especially in Group A. Our data supports the perspective of optimizing radiotherapeutic strategy based on nodal response. • CN3c breast cancer with SCLN cCR and ALN pCR after PST are potentially curable. • Nodal response to PST is an independent prognostic factor for cN3c breast cancer. • SCLN non-cCR, HR-negative, or HER2-positive patient may benefit from SCV boost. [ABSTRACT FROM AUTHOR]

Survival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer. Patients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test. In total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%–77%) and 61% (95%CI: 55%–67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378–4.632) and OS (HR: 2.173; 95%CI: 1.367–4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs. Quantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer. [ABSTRACT FROM AUTHOR]

We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4 weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61 weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013–1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214–2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status. • Postoperative pre-radiotherapy enhancing tumour volume is associated with survival. • MGMT promoter methylation is significantly associated with better survival. • Irrespective of MGMT methylation status patients benefit from lower tumour burden. [ABSTRACT FROM AUTHOR]

Melanomas frequently harbour somatic mutations in BRAF (40%) or NRAS (20%). Impact of NRAS mutations on the therapeutic outcome of immune checkpoint inhibitors (ICI) remains controversial. Potential correlation of the NRAS mutational status and programmed cell death ligand-1 (PD-L1) expression in melanoma is unknown. Advanced, non-resectable melanoma patients with known NRAS mutation status treated with first-line ICI between 06/2014 and 05/2020 in the prospective multicenter skin cancer registry ADOREG were included. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to NRAS status were analysed. A multivariate Cox model was used to analyse factors associated with PFS and OS; survival was analysed using the Kaplan–Meier approach. Among 637 BRAF wild-type patients, 310 (49%) had an NRAS mutation with Q61R (41%) and Q61K (32%). NRAS -mutated (NRAS mut) melanomas were significantly more often located on the lower extremities and trunk (p = 0.001); nodular melanoma was the most common subtype (p < 0.0001). No significant differences were found for PFS and OS for anti-PD1 monotherapy (2-year PFS 39%, [95% confidence interval (CI), 33–47] in NRAS mut patients and 41% [95% CI, 35–48] in NRAS -wild type (NRAS wt) patients; 2-year OS was 54% [95% CI, 48–61] in NRAS mut patients and 57% [95% CI, 50–64] in NRAS wt patients) and anti-PD1 plus anti-CTLA4 therapy between both cohorts (2-year PFS was 54% [95% CI, 44–66] in NRAS mut patients and 53% [95% CI, 41–67] in NRAS wt patients; 2-year OS was 58% [95% CI, 49–70] in NRAS mut patients and 62% [95% CI, 51–75] in NRA Swt patients). The ORR to anti-PD1 was 35% for NRAS wt patients and 26% for NRAS mut patients and 34% compared to 32% for combinational therapy. Data on PD-L1 expression was available in 82 patients (13%). PD-L1 expression (> 5%) was not correlated to NRAS mutational status. In multivariate analysis, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance status ≥ 1, and brain metastases were significantly associated with a higher risk of death in all patients. The PFS and OS were not affected by NRAS mutational status in patients treated with anti-PD1-based ICI. Similar ORR was seen in NRAS wt and NRAS mut patients. Tumour PD-L1 expression did not correlate with NRAS mutational status. • PFS and OS were not affected by NRAS mutational status in patients treated with anti-PD1-based ICI. • Similar response rates to anti-PD1-based ICI were seen for NRAS mut and NRAS wt patients. • There was no correlation between NRAS mutation status and programmed cell death ligand-1 expression. [ABSTRACT FROM AUTHOR]

Phase I trials historically involved heavily pretreated patients (pts) with no more effective therapeutic options available and with poor expected outcomes. There are scare data regarding profile and outcomes of pts enrolled into modern phase I trials. Here, we sought to provide an overview of pts' profile and outcome into phase I trials at Gustave Roussy (GR). This is a monocentric retrospective study, including all pts enrolled into phase I trials at GR from 2017 to 2021. Data regarding pts' demographics, tumour types, investigational treatments and survival outcomes were collected. In total, 9482 pts were referred for early phase trials; 2478 pts were screened, among which 449 (18.1%) failed screening; 1693 pts finally received at least one treatment dose as part of a phase I trial. Median age of pts was 59 years old (range, 18–88) and most common tumour types included gastrointestinal (25.3%), haematological (15%), lung (13.6%), genitourinary (10.5%) and gynaecologic cancers (9.4%). Amongst all pts treated and evaluable for response (1634 pts), objective response rate was 15.9% and disease control rate was 45.4%. Median progression-free survival and overall survival were, respectively, 2.6 months (95% confidence interval [95% CI], 2.3; 2.8) and 12.4 months (95% CI, 11.7; 13.6). As compared with historical data, our study shows that outcomes of pts included into modern phase I trials have improved and that these trials constitute nowadays a valid and safe therapeutic option. These updated data provide facts for adapting the methodology, role and place of phase I trials over the next years. • Overall, 15.9% objective response rate and 45.4% disease control rate in phase I trials. • mPFS and mOS, respectively, of 2.6 months and 12.4 months. • Phase I trials represent a valid option for patients in oncology. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has become a standard of care in the treatment of recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). However, only a subset of patients benefit from treatment. Quantification of plasma circulating tumour DNA (ctDNA) levels and on-treatment kinetics may permit real-time assessment of disease burden under selective pressures of treatment. R/M HNSCC patients treated with systemic therapy, platinum-based chemotherapy (CT) or ICB, underwent serial liquid biopsy sampling. Biomarkers tested included ctDNA measured by CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) and markers of host inflammation measured by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Among 53 eligible patients, 16 (30%) received CT, 30 (57%) ICB [anti-PD1/L1] monotherapy and 7 (13%) combination immunotherapy (IO). Median progression-free survival (PFS) and overall survival (OS) were 2.8 months (95% CI, 1.3–4.3) and 8.2 months (95% CI, 5.6–10.8), respectively. Seven (13%) patients experienced a partial response and 21 (40%) derived clinical benefit. At baseline, median ctDNA variant allele frequency (VAF) was 4.3%. Baseline ctDNA abundance was not associated with OS (p = 0.56) nor PFS (p = 0.54). However, a change in ctDNA VAF after one cycle of treatment (ΔVAF (T1–2)) was predictive of both PFS (p < 0.01) and OS (p < 0.01). Additionally, decrease in ΔVAF identified patients with longer OS despite early radiological progression, 8.2 vs 4.6 months, hazard ratio 0.44 (95% CI, 0.19–0.87) p = 0.03. After incorporating NLR and PLR into multivariable Cox models, ctDNA ∆VAF retained an association with OS. Early dynamic changes in ctDNA abundance, after one cycle of treatment, compared to baseline predicted both OS and PFS in R/M HNSCC patients on systemic therapy. • Baseline ctDNA was not associated with progression free or overall survival (OS). • A change in ctDNA after one cycle of treatment was predictive of survival. • A decrease in ctDNA (T1-2) corresponded with longer OS despite radiological progression. • Low NLR was associated with improved OS. [ABSTRACT FROM AUTHOR]

This multi-centre prospective cohort study aimed to investigate non-inferiority in patients' overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR). Patients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses. All patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval [CI] 68–85%) after SMWA versus 76% (CI 69–82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45–66%) versus 58% (CI 50–66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689–1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01). SMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease. • Similar 3-year overall survival with thermal ablation versus hepatic resection. • Treatment-related morbidity lower while options for retreatment higher. • Thermal ablation valid treatment for resectable colorectal cancer liver metastases. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are the standard treatment in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Tumour mutational burden (TMB) is a promising biomarker for the prediction of treatment outcomes. We screened 203 patients with dMMR/MSI-H mCRC treated with an anti-PD-(L)1 (anti-Programmed-Death-(Ligand)1) plus or minus an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) agent at three Italian Academic Centers. TMB was tested by Foundation One Next Generation Sequencing assay and correlated with clinical outcomes, in the overall population and according to ICI regimen. We included 110 patients with dMMR/MSI-H mCRC. Eighty patients received anti-PD-(L)1 monotherapy and 30 received anti-CTLA-4 combinations. Median TMB was 49 mut/Mb (range: 8–251 mut/Mb). The optimal prognostic cut-off for progression-free survival (PFS) stratification was 23 mut/Mb. Patients with TMB ≤23 mut/Mb had significantly worse PFS (adjusted Hazard Ratio [aHR] = 4.26, 95% confidence interval [CI]:1.85–9.82, p = 0.001) and overall survival (OS) (aHR = 5.14, 95% CI: 1.76–14.98, p = 0.003). Using a cut-off optimised for predicting treatment outcome, anti-CTLA-4 combination was associated with a significant PFS/OS benefit versus anti-PD-(L)1 monotherapy in patients with TMB>40 mut/Mb (2-year PFS: 100.0% versus 70.7%, p = 0.002; 2-year OS: 100.0% versus 76.0%, p = 0.025), but not in those with TMB ≤40 mut/Mb (2-year PFS: 59.7% versus 68.6%, p = 0.888; 2-year OS: 80.0% versus 81.0%, p = 0.949). Patients with dMMR/MSI-H mCRC and relatively lower TMB value displayed early disease progression when receiving ICIs, whereas patients with the highest TMB values may obtain the maximal benefit from intensified anti-CTLA-4/PD-1 combination. [Display omitted] • The TMB stratifies the outcomes of dMMR/MSI-H mCRC receiving ICIs. • Patients with a low TMB has poor outcomes regardless of the ICI type. • Patients with the highest TMB have greater benefit from anti-CTLA-4 combos. • TMB could be used to drive future research projects and trials' design. [ABSTRACT FROM AUTHOR]

Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov , EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease. [ABSTRACT FROM AUTHOR]

Anal cancer (AC) is a rare disease with scarce evidence from developing countries. We performed a population-based cohort study to investigate the relationship between tumor, patient, and social determinants of health with treatment outcomes of AC treated by chemoradiation (CRT). Patients who received a diagnosis of AC from 1999 to 2020 were identified from the Fundação Oncocentro de São Paulo database. Only patients with AC stage I-III treated by CRT were included. Age, sex, tumor category (T), nodal category (N), education level, practice setting, time to radiation therapy, histology, and treatment local data were extracted. With the Cox proportional hazard model, the hazard ratio and 95% confidence interval were used to test the relationship between tumor, patient, and social factors with overall survival (OS) and cancer-specific survival (CSS). With 1462 patients assessed, the median follow-up was 72 months, and the OS and CSS at 5/10 years were 61%/46% and 67%/60%, respectively. In the univariate analysis, T category, N category, sex, practice setting, and education level were associated with OS and CSS (P <.05). In the multivariate analysis, female sex, T1/2 category, N0 category, and private service were independently associated with OS (P <.05). For CSS, female sex, T1/2 category, private service, and N0 category remained significant (P <.05). CRT produced satisfactory rates of OS and CSS in patients with AC, with tumor, patient, and social determinants of health influencing the outcomes. These data could help mitigate the effects of social distortions on the survival of AC. [ABSTRACT FROM AUTHOR]

Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3–T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3–T4 status and/or intermediate/high histological grade. • The 5-year OS and DFS were 92.8% and 76.2%, respectively. • Male sex, higher T/N status, and high grade were independently associated with a worse DFS. • T3–T4 status and intermediate/high histological grade were associated with N+ status. • After PS matching, prophylactic ND was associated with a trend toward a better DFS. [ABSTRACT FROM AUTHOR]