Radiation plays an important role in the treatment of many solid tumors. While conventional fractionation schedules are commonly used, technological advances have allowed safer and more effective dose escalation in the treatment of both primary as well as metastatic lesions. There is growing evidence about the intricate role played by the immune system in modulating the effect of cancer treatment, and several pre-clinical and clinical studies have explored the use of immunotherapy in the treatment of various cancers, both in the metastatic and upfront treatment setting. This approach has shown significant success in the management of melanomas and lung cancers and has prompted exploration of the same strategy in many other cancer subtypes. Radiation has been proposed to synergize the effect of immunotherapy through various mechanisms and is currently being evaluated in various ongoing clinical trials. Several mature clinical studies have also shown significant benefit with the combination and have led to its uptake in routine clinical practice. Furthermore, the use of hypo-fractionated high-dose radiation or Stereotactic Body Radiation Treatment (SBRT) regimens have shown benefits over conventional radiation in this context and are being actively explored as a treatment strategy.

Precision healthcare aims to tailor disease prevention and early detection to individual risk. Prostate cancer screening may benefit from genomics-informed approaches. We developed and validated the P-CARE model, a prostate cancer risk prediction tool combining a polygenic score, family history and genetic ancestry, using data from over 585,000 male participants in the Million Veteran Program. The model was externally validated in diverse cohorts and implemented via a blended genome–exome assay for clinical use. Here we show that the P-CARE model identifies clinically meaningful gradients of prostate cancer risk among men, with higher scores associated with increased risk of any, metastatic and fatal prostate cancer. The model is now being used in a clinical trial of precision prostate cancer screening. This work demonstrates the potential for genomics-enabled health systems to improve prostate cancer screening and prevention in men. ClinicalTrials.gov registration: NCT05926102 . Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

PURPOSE:Breast conserving surgery (BCS) is the primary treatment for early-stage breast cancer(EBC). Typically, adjuvant endocrine therapy (ET) and radiation therapy (RT) are standard treatments offered for EBC. However, non-compliance and toxicity remain as issues with HT and many patients choose adjuvant RT alone. The benefit of adjuvant RT alone in women with low-risk EBC remains unclear. It is hypothesized that adjuvant RT-alone can improve outcomes in low-risk EBC patients, similar to ET alone or RT + ET combination. METHODS:This population-based study identified women aged 50-80 with T1, N0, Estrogen receptor positive (ER + ve), human epidermal growth receptor-2 negative(Her-2/neu-ve) EBC treated with BCS, followed by adjuvant treatments (RT-alone, ET-alone, or RT + ET combination) from 2010 to 2015. Primary outcomes were recurrence free survival (RFS), overall survival (OS), and breast cancer specific survival (BCSS). RESULTS:2810 patients were identified. Median follow-up was 73 months(Interquartile Q1,Q3:55.0,91.6). Adjuvant treatments were: BCS only 216 (8 %), RT alone 803 (29 %), ET alone 274 (10 %), and RT + ET combination 1517 (54 %). 398 patients (22.2 %) completed 5-years of ET. Compared to BCS alone, there was no statistically significant difference between treatment groups for RFS and BCSS. There were significant difference among the treatment groups for OS compared to BCS alone: Hazard ratio (HR) 0.66 (95 % confidence interval (CI): 0.45 - 0.97) for RT alone, 0.55 (95 % CI: 0.35 - 0.87) for ET alone, and 0.48 (95 % CI: 0.33 - 0.70) for RT + ET combination. Determinants of OS were age, tumor grade, comorbidities, and adjuvant therapy. CONCLUSIONS:Our population-based cohort study showed that there was no statistically significant difference in RFS and BCSS among various adjuvant treatments versus BCS alone. However, RT alone, ET alone and RT + ET combination resulted in a statistically significant improvement in OS compared to BCS alone. Our findings support RT alone can be a viable alternative to ET + RT combination for women over 50 with low-risk EBC. Ongoing studies like EUROPA, REaCT trial and EPOPE will provide more insight into the role of RT alone as a definite treatment option.

Adjuvant radiotherapy (RT) is an essential component of the optimal management of breast cancer (BC). However, RT-induced risk of cardiac toxicity is a major concern for patients with left sided BC as they are at twice the risk compared to right sided BC. Modern RT-planning techniques that include deep inspiratory breath holding (DIBH) have the potential to mitigate radiation associated cardiotoxicity. To evaluate the impact of DIBH on cardiac magnetic resonance (CMR) measures of cancer therapy related cardiac dysfunction (CTRCD) in women with left sided breast cancer treated with adjuvant RT in a phase II clinical trial. Eligible patients underwent either free breathing (FB) or DIBH treatment delivery, if the predicted mean heart RT dose was <5 Gy or >5 Gy, respectively. Those eligible for DIBH and FB RT without prior exposure to anthracyclines or trastuzumab (CH) were allocated to cohort I and II respectively, and those receiving DIBH RT with prior exposure to CH were placed in cohort III. Non-contrast CMR scans were acquired at pre-RT and at 16 weeks and 52 weeks post completion of RT to assess left ventricular ejection fraction (LVEF) and LV global longitudinal strain (GLS). CTRCD was defined according to ESC 2022 Cardio-Oncology guidelines with asymptomatic moderate CTRCD defined as a new reduction in LVEF by ≥ 10% to an LVEF of 40-49% and mild CTRCD defined as LVEF ≥ 50% and a new reduction in GLS > 15% from baseline. Change in LV function and CTRCD were compared between groups at 16 and 52 weeks using ANOVA or Chi-square statistics. 25 patients received DIBH-RT (cohort 1), 21 received FB-RT (cohort II) and 23 had adjuvant CH prior to DIBH-RT (cohort III). There were significant age differences between cohorts, but baseline LVEF and LV GLS were not significantly different (Table). Mean and maximum heart and LV radiation doses were similar between cohorts (Table). There were no significant changes in LVEF at 16 and 52 weeks and no cases of asymptomatic moderate CTRCD in any of the cohorts. At 16 weeks, mean LV GLS was similar between cohorts but improved from baseline in cohort 1 relative to cohorts 2 and 3, -4.6 ± 15.4% vs. +9.8 ± 8.9 and +4.2 ± 15.4, respectively, p=0.004 (Table, Figure). There were also no cases of mild CTRCD at 16 weeks in cohort 1 compared to 5 in cohort 2 and 6 in cohort 3, p=0.034. The observed group differences in LV GLS and mild CTRCD persisted at 52 weeks. On multivariable regression analysis, baseline LV GLS and maximum heart radiation dose were significant predictors of change in LV GLS at 16 weeks. In patients with left-sided breast cancer, mild CTRCD was observed in patients exposed to FB-RT or DIBH-RT plus chemotherapy but not following DIBH-RT alone. Factors predicting change in LV GLS included baseline LV GLS and maximum heart radiation dose.Table Figure

Background: Stereotactic body radiotherapy (SBRT) is an evolving treatment for the local management of pancreatic cancer (PC). The main purpose of this study is to report our initial experience in terms of local control (LC) and toxicity for PC patients treated with SBRT. Methods: We conducted a retrospective review of patients treated with SBRT using abdominal compression (AC) or an end-expiratory breath-holding (EEBH) technique. The median prescribed dose was 35 Gy, delivered in five fractions. Toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and survival was estimated using the Kaplan–Meier method. Results: From 2017 to 2023, 17 PC patients were offered SBRT. Their median age was 69 years. The median follow-up from the date of diagnosis was 22.37 months. The overall survival (OS) was 94% at 1 year and 60.9% at 2 years. The progression-free survival (PFS) was 63.1% at 6 months and 56.1% at 9 months. The median OS was 26.3 months, and the median PFS was 20.6 months. The 6-month and 1-year LC rates were 71% and 50.8%, respectively. Conclusion: We are successful in implementing the SBRT program at our centre. SBRT appears to be a promising treatment option for achieving LC with limited acute toxicities.

PurposeWe report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM).MethodsIn this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS).Results451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc.ConclusionsOur analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry ( P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

PURPOSE:Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer.METHODS AND MATERIALS:Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared.RESULTS:For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months.CONCLUSIONS:Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.

MR-based radiomics predict LC post-SBRT in patients with malignant liver tumors. Further research focused on independent validation of the model is required to explore its clinical use.

Aim: To determine the efficacy of preoperative chemoradiotherapy as per the CROSS protocol for oesophageal/gastroesophageal junction cancer (OEGEJC), when expanded to patients outside of the inclusion/exclusion criteria defined in the original clinical trial. Materials and methods: Data were collected retrospectively on 229 OEGEJC patients referred for curative-intent preoperative chemoradiotherapy. Outcomes including pathological complete response (pCR), overall survival (OS), cancer-specific survival and recurrence-free survival (RFS) of patients who met CROSS inclusion criteria (MIC) versus those who failed to meet criteria (FMIC) were determined. Results: In total, 42.8% of patients MIC, whereas 57.2% FMIC; 16.6% of patients did not complete definitive surgery. The MIC cohort had higher rates of pCR, when compared with the FMIC cohort (33.3% versus 20.6%, P = 0.039). The MIC cohort had a better RFS, cancer-specific survival and OS compared with the FMIC cohort (P = 0.006, P = 0.004 and P = 0.009, respectively). Age >75 years and pretreatment weight loss >10% were not associated with a poorer RFS (P = 0.541 and 0.458, respectively). Compared with stage I-III patients, stage IVa was associated with a poorer RFS (hazard ratio (HR) = 2.158; 95% confidence interval (CI) = 1.339-3.480, P = 0.001). Tumours >8 cm in length or >5 cm in width had a trend towards worse RFS (HR = 2.060; 95% CI = 0.993-4.274, P = 0.052). Conclusion: Our study showed that the robust requirements of the CROSS trial may limit treatment for patients with potentially curable OEGEJC and can be adapted to include patients with a good performance status who are older than 75 years or have >10% pretreatment weight loss. However, the inclusion of patients with celiac nodal metastases or tumours >8 cm in length or >5 cm in width may be associated with poor outcomes. Crown Copyright (C)2022 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

AIMS:18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is routinely used for the pre-treatment staging of oesophageal or gastro-oesophageal junction cancers (EGEJC). The aim of this study was to identify objective 18FDG-PET/CT-derived parameters that can aid in predicting the patterns of recurrence and prognostication in patients with EGEJC. PATIENTS AND METHODS:EGEJC patients referred for consideration of preoperative chemoradiation therapy were identified and clinicopathological data were collected. 18FDG-PET/CT imaging data were reviewed and correlated with treatment outcomes. Maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis were assessed and association with recurrence-free survival (RFS), locoregional recurrence-free survival (LR-RFS), oesophageal cancer-specific survival (ECSS) and overall survival were evaluated using receiver operating characteristic curves, as well as Cox regression and Kaplan-Meier models. RESULTS:In total, 191 EGEJC patients completed trimodality treatment and 164 with 18FDG-PET/CT data were included in this analysis. At the time of analysis, 15 (9.1%), 70 (42.7%) and two (1.2%) patients were noted to have locoregional, distant and both locoregional and distant metastases, respectively. The median RFS was 30 months (9.6-50.4) and the 5-year RFS was 31.1%. The 5-year overall survival and ECSS were both noted to be 34.8%. Pre-treatment MTV25 > 28.5 cm3 (P = 0.029), MTV40 > 12.4 cm3 (P = 0.018) and MTV50 > 10.2 cm3 (P = 0.005) predicted for worse LR-RFS, ECSS and overall survival for MTV definition of voxels ≥25%, 40% and 50% of SUVmax. CONCLUSION:18FDG-PET/CT parameters MTV and total lesion glycolysis are useful prognostic tools to predict for LR-RFS, ECSS and overall survival in EGEJC. MTV had the highest accuracy in predicting clinical outcomes. The volume cut-off points we identified for different MTV thresholds predicted outcomes with significant accuracy and may potentially be used for decision making in clinical practice.

Objectives: Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM. Materials and Methods: In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis. Tumor volumes were derived from pretreatment MRI. Clinical parameters such as tumor volume, stage, and location were analyzed by univariate and multivariate analysis, against pCR. A receiver operator characteristic curve was generated to identify a tumor volume cut-off with the highest clinically relevant Youden index for predicting pCR. Results: Seventy-five of 412 patients (18%) achieved pCR. A tumor volume threshold of 37.3 cm(3) was identified as predictive for pCR. On regression analysis, a tumor volume >37.3 cm(3) was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV <37.3 cm(3) [odds ratio (OR)=3.7, P<0.0001] was significantly associated with an increased pCR rate, whereas tumor length > 4.85 cm was associated with pCR on univariate (OR=3.03, P<0.01) but not on multivariate analysis (OR=1.45, P=0.261). Other clinical parameters did not impact pCR rates. Conclusions: A tumor volume threshold of 37.3 cm(3) was identified as predictive for pCR in locally advanced rectal cancer patients receiving neoadjuvant chemoradiation. Tumors above this volume threshold corresponded to a greater than 78% probability of not achieving pCR. This information will be helpful at diagnosis for clinicians who are considering potential candidates for NOM.

An educational session related to the Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held virtually on 14 October 2020. The WCGCCC is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba), who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists, radiologists, and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of total neoadjuvant therapy in rectal cancer.