Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC.

BACKGROUND: The role of tyrosine kinase inhibitors (TKIs) in early-stage and metastatic oncogene-driven non-small cell lung cancer (NSCLC) is established, but it remains unknown how best to integrate TKIs with concurrent chemoradiotherapy (cCRT) in locally advanced disease. The phase 2 ASCENT trial assessed the efficacy and safety of afatinib and cCRT with or without surgery in locally advanced epidermal growth factor receptor (EGFR)-mutant NSCLC. PATIENTS AND METHODS: Adults ≥18 years with histologically confirmed stage III (AJCC 7th edition) NSCLC with activating EGFR mutations were enrolled at Mass General and Dana-Farber/Brigham Cancer Centers, Boston, Massachusetts. Patients received induction afatinib 40 mg daily for 2 months, then cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 IV every 3 weeks during RT (definitive or neoadjuvant dosing). Patients with resectable disease underwent surgery. All patients were offered consolidation afatinib for 2 years. The primary endpoint was the objective response rate (ORR) to induction TKI. Secondary endpoints were safety, conversion to operability, progression-free survival (PFS), and overall survival (OS). Analyses were performed on the intention-to-treat population. RESULTS: Nineteen patients (median age 56 years; 74% female) were enrolled. ORR to induction afatinib was 63%. Seventeen patients received cCRT; 2/9 previously unresectable became resectable. Ten underwent surgery; 6 had a major or complete pathological response. Thirteen received consolidation afatinib. With a median follow-up of 5.0 years, median PFS and OS were 2.6 (95% CI, 1.4-3.1) and 5.8 years (2.9-NR), respectively. Sixteen recurred or died; 6 recurrences were isolated to CNS. The median time to progression after stopping consolidation TKI was 2.9 months (95% CI, 1.1-7.2). Four developed grade 2 pneumonitis. There were no treatment-related deaths. CONCLUSION: We explored the efficacy of combining TKI with cCRT in oncogene-driven NSCLC. Induction TKI did not compromise subsequent receipt of multimodality therapy. PFS was promising, but the prevalence of CNS-only recurrences and rapid progression after TKI discontinuation speak to unmet needs in measuring and eradicating micrometastatic disease.

The Role of Axillary Lymph Node Dissection versus Sentinel Lymph Node Dissection in Breast Cancer Patients with Clinical N2b-N3c Disease Who Receive Adjuvant Radiotherapy.

BACKGROUND: For breast cancer with advanced regional lymph node involvement, axillary lymph node dissection (ALND) remains the standard of care for staging and treating the axilla despite the presence of undissected lymph nodes. The benefit of ALND in this setting is unknown. OBJECTIVES: We sought to describe national patterns of care of axillary surgery and its association with overall survival (OS) among women with cN2b-N3c breast cancer who receive adjuvant radiotherapy. PATIENTS AND METHODS: We identified female patients with cN2b-N3c breast cancer from 2012 to 2017 from the National Cancer Database. Clinical and demographic information were analyzed using Wilcoxon rank sum and χ2 tests. Predictors of receipt of ALND and predictors of death were identified with multivariable logistic regression modeling. Inverse probability of treatment weighting was implemented to adjust for differences in treatment cohorts. The Kaplan-Meier method was used to evaluate OS. RESULTS: We identified 7167 patients. Of these, 922 (13%) received SLNB and 6254 (87%) received ALND; 7% were cN2b, 19% cN3a, 24% cN3b, 19% cN3c, and 31% cN3, not otherwise specified. Predictors of receipt of ALND were age 50-69 years [odds ratio (OR) 1.3, p < 0.01], cN3a (OR 7.6, p < 0.01), cN3b (OR 2.8, p < 0.01), and cN3c (OR 4.2, p < 0.01). Predictors of death included cN3c (OR 1.9, p < 0.01), age 70-90 years (OR 1.5, p = 0.01), and positive surgical margins (OR 1.5, p < 0.01). After cohort balancing, ALND was not associated with improved OS when compared with SLNB (HR 0.99, p = 0.91). CONCLUSIONS: ALND in patients with advanced nodal disease was not associated with improved survival compared with SLNB for women who receive adjuvant radiotherapy.

Principles of artificial intelligence in radiooncology.

PURPOSE: In the rapidly expanding field of artificial intelligence (AI) there is a wealth of literature detailing the myriad applications of AI, particularly in the realm of deep learning. However, a review that elucidates the technical principles of deep learning as relevant to radiation oncology in an easily understandable manner is still notably lacking. This paper aims to fill this gap by providing a comprehensive guide to the principles of deep learning that is specifically tailored toward radiation oncology. METHODS: In light of the extensive variety of AI methodologies, this review selectively concentrates on the specific domain of deep learning. It emphasizes the principal categories of deep learning models and delineates the methodologies for training these models effectively. RESULTS: This review initially delineates the distinctions between AI and deep learning as well as between supervised and unsupervised learning. Subsequently, it elucidates the fundamental principles of major deep learning models, encompassing multilayer perceptrons (MLPs), convolutional neural networks (CNNs), recurrent neural networks (RNNs), transformers, generative adversarial networks (GANs), diffusion-based generative models, and reinforcement learning. For each category, it presents representative networks alongside their specific applications in radiation oncology. Moreover, the review outlines critical factors essential for training deep learning models, such as data preprocessing, loss functions, optimizers, and other pivotal training parameters including learning rate and batch size. CONCLUSION: This review provides a comprehensive overview of deep learning principles tailored toward radiation oncology. It aims to enhance the understanding of AI-based research and software applications, thereby bridging the gap between complex technological concepts and clinical practice in radiation oncology.

Deep learning for autosegmentation for radiotherapy treatment planning: State-of-the-art and novel perspectives.

The rapid development of artificial intelligence (AI) has gained importance, with many tools already entering our daily lives. The medical field of radiation oncology is also subject to this development, with AI entering all steps of the patient journey. In this review article, we summarize contemporary AI techniques and explore the clinical applications of AI-based automated segmentation models in radiotherapy planning, focusing on delineation of organs at risk (OARs), the gross tumor volume (GTV), and the clinical target volume (CTV). Emphasizing the need for precise and individualized plans, we review various commercial and freeware segmentation tools and also state-of-the-art approaches. Through our own findings and based on the literature, we demonstrate improved efficiency and consistency as well as time savings in different clinical scenarios. Despite challenges in clinical implementation such as domain shifts, the potential benefits for personalized treatment planning are substantial. The integration of mathematical tumor growth models and AI-based tumor detection further enhances the possibilities for refining target volumes. As advancements continue, the prospect of one-stop-shop segmentation and radiotherapy planning represents an exciting frontier in radiotherapy, potentially enabling fast treatment with enhanced precision and individualization.

Successful implementation of online educational lectures of the German Society for Radiation Oncology (DEGRO).

PURPOSE: Modern digital teaching formats have become increasingly important in recent years, in part due to the COVID-19 pandemic. In January 2021, an online-based webinar series was established by the German Society for Radiation Oncology (DEGRO) and the young DEGRO (yDEGRO) working group. In the monthly 120-minute courses, selected lecturers teach curricular content as preparation for the board certification exam for radiation oncology. METHODS: The evaluation of the 24 courses between 01.2021 and 12.2022 was performed using a standardized questionnaire with 21 items (recording epidemiological characteristics of the participants, didactic quality, content quality). A Likert scale (1-4) was used in combination with binary and open-ended questions. RESULTS: A combined total of 4200 individuals (1952 in 2021 and 2248 in 2022) registered for the courses, and out of those, 934 participants (455 in 2021 and 479 in 2022) later provided evaluations for the respective courses (36% residents, 35% specialists, 21% medical technicians for radiology [MTR], 8% medical physics experts [MPE]). After 2 years, 74% of the DEGRO Academy curriculum topics were covered by the monthly webinars. The overall rating by participants was positive (mean 2021: 1.33 and 2022: 1.25) and exceeded the curriculum offered at each site for 70% of participants. Case-based learning was identified as a particularly well-rated method. CONCLUSION: The DEGRO webinar expands the digital teaching opportunities in radiation oncology. The consistently high number of participants confirms the need for high-quality teaching and underlines the advantages of e­learning methods. Optimization opportunities were identified through reevaluation of feedback from course participants. In its design as a teaching format for a multiprofessional audience, the webinar series could be used as a practice model of online teaching for other disciplines.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

PURPOSE: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.

Friedrich Dessauer (1881-1963): the forgotten medical physicist, politician, and philosopher.

Today, the name Friedrich Dessauer is almost forgotten; however, his scientific, social, and political works should not be. Dessauer's professional career began at a young age as a professor of physics in Frankfurt am Main. It is said that he published 400 papers and 65 book chapters and pamphlets. He was a technical inventor who established laws that dealt with theories to explain the limited understanding of the effects of radiation on cells. He advocated for methods to improve the therapeutic ratio. As a devout Catholic politician, Dessauer was an early opponent of National Socialism. This led to him being thrown into prison for political reasons in 1933. He did not leave until 1934, and then for Istanbul, largely thanks to Turkish efforts and his appointment as director of a large new institution. While he was already a well-known physicist in Germany, he had to start from scratch in order to build a modern institute. A recent article in the journal Radiotherapy and Oncology celebrated his important contributions to radiology from Turkey. After his contract in Istanbul expired in 1937, he left for the small University of Fribourg in Switzerland, where he was unfortunately unable to continue his scientific productivity. Dessauer wrote textbooks as well as political and philosophical books, and attempted to bridge the gap between Catholicism and science. Additionally, after the war, he began to teach again in Frankfurt. In photos of Dessauer, radiation-induced skin changes on his face and hands were clearly visible. Towards the end of his life, he received many medals and honors for his achievements in Germany, some of them posthumously.

Dose prescription for stereotactic body radiotherapy: general and organ-specific consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery.

PURPOSE AND OBJECTIVE: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. MATERIALS AND METHODS: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60-79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. RESULTS: Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60-79% consensus. CONCLUSION: In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT.

German radiation oncology's next generation: a web-based survey of young biologists, medical physicists, and physicians-from problems to solutions.

BACKGROUND: Radiation science is of utmost significance not only due to its growing importance for clinical use, but also in everyday life such as in radiation protection questions. The expected increase in cancer incidence due to an aging population combined with technical advancements further implicates this importance and results in a higher need for sufficient highly educated and motivated personnel. Thus, factors preventing young scientists and medical personnel from entering or remaining in the field need to be identified. METHODS: A web-based questionnaire with one general and three occupation-specific questionnaires for physicians, biologists, and medical physicists working in radiation oncology and research was developed and circulated for 6 weeks. RESULTS: While the overall satisfaction of the 218 participants was quite high, there are some points that still need to be addressed in order to ensure a continuing supply of qualified personnel. Among these were economic pressure, work-life balance, work contracts, protected research time, and a demand for an improved curriculum. CONCLUSION: Mentoring programs, improved education, and strengthening the value of societies in radiation sciences as well as translational approaches and more flexible working arrangements might ensure a high-quality workforce and thus patient care in the future.

Localized Merkel cell carcinoma treatment considerations: a response to the forty-year experience at the Peter MacCallum cancer centre.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin with poor prognosis and rising global incidence. A recently published article in BMC Cancer, titled "Merkel cell carcinoma: a forty-year experience at the Peter MacCallum Cancer Centre" (Wang et al.), provides a contemporary analysis of locoregional disease outcomes in Australia which highlights the comparative effectiveness of radiotherapy for excisions with involved margins versus wide local excision. There is a persistent lack of clear, well-defined guidelines to manage MCC in Australia despite experiencing the highest rates globally. The advanced age at onset also provides inherent challenges for optimal management and often, a case-by-case approach is necessary based on patient preferences, baseline function and fitness for surgery. This paper responds to the recently published article by Wang et al. and will expand the discourse regarding management of localized MCC. Specifically, we will discuss the surgical excision approaches; alternative treatment options for MCC including radiotherapy, Mohs micrographic surgery and novel immunotherapy agents being investigated through several clinical trials.

PErspective and current status of Radiotherapy Service in IRan (PERSIR)-1 study: assessment of current external beam radiotherapy facilities, staff and techniques compared to the international guidelines.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

Management of patients with diffuse intrinsic pontine glioma in Australia and New Zealand: Australian and New Zealand Children's Haematology/Oncology Group position statement.

INTRODUCTION: The main mission of the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) is to develop and facilitate local access to the world's leading evidence-based clinical trials for all paediatric cancers, including brain tumours, as soon as practically possible. Diffuse intrinsic pontine gliomas (DIPGs) - a subset of a larger group of tumours now termed diffuse midline glioma, H3K27-altered (DMG) - are paediatric brain cancers with less than 10% survival at two years. In the absence of any proven curative therapies, significant recent advancements have been made in pre-clinical and clinical research, leading many to seek integration of novel therapies early into standard practice. Despite these innovative therapeutic approaches, DIPG remains an incurable disease for which novel surgical, imaging, diagnostic, radiation and systemic therapy approaches are needed. MAIN RECOMMENDATIONS: All patients with DIPG should be discussed in multidisciplinary neuro-oncology meetings (including pathologists, neuroradiologists, radiation oncologists, neurosurgeons, medical oncologists) at diagnosis and at relapse or progression. Radiation therapy to the involved field remains the local and international standard of care treatment. Proton therapy does not yield a superior survival outcome compared with photon therapy and patients should undergo radiation therapy with the available modality (photon or proton) at their treatment centre. Patients may receive concurrent chemotherapy or radiation-sensitising agents as part of a clinical trial. Biopsy should be offered to facilitate consideration of experimental therapies and eligibility for clinical trial participation. After radiation therapy, each patient should be managed individually with either observation or considered for enrolment on a clinical trial, if eligible, after full discussion with the family. Re-irradiation can be considered for progressive disease. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: Every child diagnosed with DIPG should be offered enrolment on a clinical trial where available. Access to investigational drugs without biological rationale outside the clinical trial setting is not supported. In case of potentially actionable target identification with molecular profiling and absence of a suitable clinical trial, rational targeted therapies can be considered through compassionate access programs.

Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile.

Aim: To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART).Materials & methods: Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event.Results: Random sampling of matched patient pairs (n = 52 ART-treated; 371 no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1.Conclusion: The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1).

Independent validation study: 40-GEP identifies patients with cutaneous squamous cell carcinoma who would be most likely to benefit from adjuvant radiation therapy.

Prehabilitation in radiation therapy: a scoping review.

PURPOSE/OBJECTIVES: Radiation therapy (RT) is a central component of cancer treatment with survival and long-term quality-of-life benefits across a spectrum of oncologic diagnoses. However, RT has been associated with varying levels of fatigue, pain, weight loss, and changes in mental health both during and post-treatment. Prehabilitation aims to optimize health prior to anti-neoplastic therapy in order to reduce side effects, increase adherence to treatment, expedite post-treatment recovery, and improve long-term outcomes. Though prehabilitation has been studied in those undergoing cancer-related surgery, literature on prehabilitation in individuals undergoing RT has not been comprehensively explored. Thus, this scoping review aims to summarize the existing literature focused on prehabilitation interventions for patients receiving RT. MATERIALS/METHODS: The PRISMA-ScR checklist for conducting scoping reviews was adopted to identify and evaluate studies investigating the efficacy of prehabilitation before and during RT for cancer over the past 21 years (10/2002-10/2022). A search of prehabilitation and RT was performed to identify studies investigating prehabilitation interventions in adult cancer patients undergoing RT. RESULTS: A total of 30 articles met inclusion criteria, yielding 3657 total participants. Eighteen (60%) studies were randomized controlled trials (RCTs) with sample sizes ranging from 21 to 221. The most commonly studied populations were patients with head and neck cancer, followed by rectal, breast, and lung cancer. A majority (80%) of studies evaluated one prehabilitation intervention (i.e., unimodal). Targeted physical exercises were the most common intervention, followed by general physical exercises and technology/apps. Adherence/feasibility was the most common primary outcome, representing 30% of studies. All studies reported data on sex, and 5 (17%) reported data on race and/or ethnicity. CONCLUSIONS: Prehabilitation interventions have been successfully implemented in patients with cancer undergoing surgical treatment. Based on limited current literature, prehabilitation appears to have a promising effect in reducing morbidity in adult cancer patients requiring RT. Though our review identified many RCTs, they were frequently small sample trials with primary outcomes focused on feasibility, rather than functional status or quality of life. Thus, there is a need for adequately powered, randomized controlled intervention trials to investigate the efficacy of prehabilitation and maximize the treatment outcomes for patients undergoing RT.

RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials.

OBJECTIVE: To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy. METHODS: Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment. RESULTS: Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%). CONCLUSIONS: The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

Adjuvant external beam radiotherapy combined with brachytherapy for intermediate-risk cervical cancer.

OBJECTIVE: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer. METHODS: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 cm or ranging from 2 to 4 cm with lymphovascular space invasion (LVSI) were included. Patients with distant metastasis or parametrial involvement were excluded. Patients who underwent EBRT alone were compared with those who also received brachytherapy after 2:1 propensity score matching. RESULTS: In total, 1174 patients met the inclusion criteria, and 26.7% of them received brachytherapy. After 2:1 propensity score matching, we included 620 patients in the EBRT group and 312 in the combination treatment group. Patients who received brachytherapy had higher equivalent doses than those only receiving EBRT. Overall survival did not differ between the two groups (hazard ratio (HR) 0.88 (95% confidence interval (CI), 0.62 to 1.23]; p=0.45). After stratification according to tumor histology, LVSI, and surgical approach, brachytherapy was not associated with improved overall survival. However, in patients who did not receive concomitant chemotherapy, the overall survival rate for those receiving EBRT and brachytherapy was significantly higher than that for those receiving EBRT alone (HR, 0.48 (95% CI, 0.27 to 0.86]; p=0.011). CONCLUSION: About one-fourth of the study patients received brachytherapy and EBRT. The variability in the doses and radiotherapy techniques used highlights treatment heterogeneity. Overall survival did not differ for EBRT with and without brachytherapy. However, overall survival was longer for patients who received brachytherapy but did not receive concomitant chemotherapy.

Malnutrition is associated with poor survival in women receiving radiotherapy for cervical cancer.

OBJECTIVE: Cancer patients are at risk of malnutrition, which is associated with poor oncological outcomes. The aim of this study was to assess the incidence of malnutrition before, during, and after radiotherapy in locally advanced cervical cancer patients. In addition, we evaluated the impact of malnutrition on survival, and whether and when malnourished patients were referred to a dietitian. METHODS: This retrospective cohort study included cervical cancer patients who received primary or adjuvant radiotherapy with curative intent between January 2013 and January 2021. Patient and treatment characteristics, including longitudinal data on weight and dietary care, were retrieved from the electronic patient files. Malnutrition was defined by body mass index and weight loss according to the Global Leadership Initiative on Malnutrition (GLIM). Overall survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression analysis was used to estimate hazard ratios for key prognostic factors. RESULTS: A total of 294 patients were included. Median follow-up was 40 months (range 7-101 months). Malnutrition occurred in 44 patients (15%) at baseline, in 132 (45%) during radiotherapy, and in 63 (21%) during follow-up. Referral to a dietician occurred in 45% of the 138 patients who were malnourished before or during radiotherapy. Malnutrition was significantly associated with worse survival after adjusting for age, performance score, diabetes, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and nodal stage. The 3 year overall survival in patients with malnutrition was 77% (95% confidence interval (CI) 70% to 85%) and without malnutrition 89% (95% CI 83% to 95%); p=0.001). Independent significant risk factors for worse overall survival were: malnutrition, age ˃52 years, adenocarcinoma, FIGO stage III/IV, and N1 disease. CONCLUSION: Malnutrition was common in cervical cancer patients treated with radiotherapy and was associated with a shorter overall survival. Further studies are needed to evaluate the effectiveness of better monitoring of malnutrition and faster and better dietary intervention on survival and quality of life.

Molecular biology as a driver in therapeutic choices for ovarian cancer.

The majority of patients with ovarian cancer relapse within 3 years of first line chemotherapy. Therefore, choosing the most appropriate treatment in the recurrence setting has a fundamental role in defining a patient's prognosis. Treatment options include systemic and intra-peritoneal chemotherapy, secondary cytoreductive surgery, and stereotactic body radiotherapy. The best therapeutic choice depends on multiple factors and not only on treatment-free interval. For systemic therapy, prior lines therapy, residual toxicities, comorbidities, performance status, and patient preferences should be taken into account. Secondary cytoreductive surgery can be proposed in patients in which complete tumor resectability can be predicted and in those with oligometastatic disease. Stereotactic body radiotherapy represents a valid alternative to surgery for oligometastatic disease with high local control and minimal toxicity. Current evidence has demonstrated an emerging role of BRCA mutational status and molecular profiling in the impacting response to systemic and local treatments. Therefore, these could provide guidance in the treatment decision process and help identify patients who respond better to poly(ADP-ribose) polymerase (PARP)-inhibitors or immunotherapy or to a combined approach with surgery rather than to platinum-based chemotherapy. Current knowledge in this field could help widen therapeutic options, especially for platinum-resistant patients. In this review, we offer an overview of the state of the art regarding the role of chemotherapy, radiotherapy, and surgery in this setting and their implications in clinical practice and in the treatment decision process, so as to provide the best tailored therapy in patients with recurrent ovarian cancer.