Search

Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.

Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation., Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature., Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up., Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients.

Purpose: Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation., Materials and Methods: Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients., Results: Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade < or = 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively., Conclusion: 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

Simple Summary: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy (HDREBT). The advantage of this treatment is allowing for better sparing of normal tissues surrounding the tumor during treatment while delivering higher dose to the tumor. This diminishes the number and severity of side effects and results in more effective treatment. This manuscript summarizes two decades of technological evolution and progress in clinical studies to validate this treatment concept from the pre-operative setting to prevent tumor recurrence and, more recently, the introduction of the objective of cure without surgery; i.e., non-operative management (NOM) for patients with curable rectal cancer. HDREBT is a conformed radiation modality, shown to be safe and efficient both in the pre-operative setting and is presently being explored with interest in NOM in a multicenter study. (1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community's work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4–6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus. Summary: Immunotherapy has less effect on the patient bone marrow compared to chemotherapy. The potential synergy between radiotherapy and immunotherapy may improve local control and survival for older patients with selected cancer. Preliminary data are encouraging because of better survival and local control in diseases which are traditionally resistant to radiotherapy and chemotherapy such as melanoma and renal cell carcinoma. Key Message: We propose a new paradigm combining immunotherapy at a reduced dose and/or extended dosing intervals and hypofractionated radiotherapy for older patients with selected cancer which needs to be tested in future clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Late gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood. Materials and Methods: The aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded. Results: A history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry. Conclusion: These results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies. [ABSTRACT FROM AUTHOR]

Organ preservation for patients diagnosed with rectal cancer is an increasingly popular treatment strategy. In this paradigm, prospective data and early results from randomized trials suggest improved success rates with endoluminal radiotherapy techniques over external beam radiotherapy counterparts. We have previously published the interim analysis of the randomized phase II-III Morpheus trial, exploring the efficacy of external beam radiotherapy boost (EBRT, Arm A) against adaptive brachytherapy boost (BT, Arm B). We aim to report the early findings from bowel function evaluation in this research patient population. This single institution, randomized phase II-III trial (Morpheus) received IRB approval and is ongoing. Patients receiving radiotherapy for rectal cancer were randomized 1:1 to Arm A, pelvic chemoradiation (CRT) with EBRT Boost, or Arm B, pelvic CRT with BT Boost. At the time of the first pre-planned interim analysis, the Lower Anterior Resection Score (LARS) quality of life surveys were queried. The available data were summarized by arm as median LARS score and interquartile range (IQR) of LARS scores. Time points consisted of baseline, 1-6, 7-12, 13-24, 25-36 months after treatment. We performed mixed effects regression analyses in order to assess time trends in LARS and compare treatment effect in both arms. We modeled the crude LARS score categories (known as "none", "minor", and "major" LARS) using univariate regression models. There were 45 patients in the Morpheus trial sub-population, who contributed 203 LARS evaluations over follow-up. The median age was 68 years, with 31 patients being male. At the time of this analysis, 20 patients had been randomized to Arm A, and 25 patients were in Arm B. Tumor location was either in the lower third (25/45, 56%) or middle third (20/45, 44%) of the rectum, based on trial inclusion criteria. The baseline LARS score was similar between arms (Arm A mean 18, Arm B mean 21). Within the first 6 months of therapy, the risk of Major LARS was significantly greater in Arm B, with 62% of patients experiencing Major symptoms versus 14% in Arm A (OR 23.9, 95% CI 2.5-226.5). However, at time points beyond 12 months, the risk of Major LARS was significantly greater in Arm A and sustained over time: for instance, at the 25-36 months bracket, 3/8 (38%) of Arm A experienced Major LARS, versus 2/13 (15%) in Arm B (OR 0.5, 95% CI 0-9.2). The sub-analysis in the Morpheus trial suggested that LARS scores and the odds of major LARS were higher in Arm B than Arm A during the 1-6 months after treatment, later reversing, with worse LARS scores in Arm A beyond 12 months. However, due to the small sample size, the confidence intervals were very large, and the statistical power to detect a difference was low. We also observed some challenges in interpreting data without accounting for the proportion of patients undergoing temporary ileostomy or permanent colostomy placement. This trial is ongoing, with plans to activate this trial in additional participating institutions, and to analyze the bowel function measures at maturity. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin–stained section prepared at the block face. One representative section for tumor was stained for factor VIII–related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200× field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200× field. Using a breakpoint of MVD <60 vs. ≥60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan–Meier method and compared by the log–rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD <60 vs. MVD ≥60. The study was perhaps limited by the small size of the NPC samples. [Copyright &y& Elsevier]