Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results.

BACKGROUND: The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. METHODS: The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. RESULTS: The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSIONS: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

Remote Monitoring and Data Collection for Decentralized Clinical Trials.

Importance: Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. Objective: To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials. Design, Setting, and Participants: The Bloomberg New Economy International Cancer Coalition, composed of patient advocacy, industry, government regulator, and academic medical center representatives, developed a survey directed to global biopharmaceutical companies of the coalition from October 1 through December 31, 2022, with a focus on registrational clinical trials. The data for this survey study were analyzed between January 1 and 31, 2023. Exposure: Adoption of decentralized clinical trial technologies. Main Outcomes and Measures: The survey measured (1) outcomes of different remote monitoring and data collection technologies on patient centricity, (2) adoption of these technologies in oncology and all therapeutic areas, and (3) barriers and facilitators to adoption using descriptive statistics. Results: All 8 invited coalition companies completed the survey, representing 33% of the oncology market by revenues in 2021. Across nearly all technologies, adoption in oncology trials lags that of all trials. In the current state, electronic diaries and electronic clinical outcome assessments are the most used technology, with a mean (SD) of 56% (19%) and 51% (29%) adoption for all trials and oncology trials, respectively, whereas visits within local physician networks is the least adopted at a mean (SD) of 12% (18%) and 7% (9%), respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 of the 11 technologies surveyed. Furthermore, digitally enabled recruitment, local imaging capabilities, and local physician networks were identified as technologies that could be most effective for improving patient centricity in the long term. Conclusions and Relevance: These findings may help to galvanize momentum toward greater adoption of enabling technologies to support a new paradigm of trials that are more accessible, less burdensome, and more inclusive.

Harnessing progress in radiotherapy for global cancer control.

The pace of technological innovation over the past three decades has transformed the field of radiotherapy into one of the most technologically intense disciplines in medicine. However, the global barriers to access this highly effective treatment are complex and extend beyond technological limitations. Here, we review the technological advancement and current status of radiotherapy and discuss the efforts of the global radiation oncology community to formulate a more integrative 'diagonal approach' in which the agendas of science-driven advances in individual outcomes and the sociotechnological task of global cancer control can be aligned to bring the benefit of this proven therapy to patients with cancer everywhere.

Extended Results and Independent Validation of a Phase 2 Trial of Metastasis-Directed Therapy for Molecularly Defined Oligometastatic Prostate Cancer.

PURPOSE: The role of metastasis-directed therapy (MDT) in molecularly defined oligorecurrent prostate cancer (PCa) remains irresolute. We present extended follow-up and an independent validation cohort of a prospective trial. METHODS AND MATERIALS: This study consists of 2 sequential single-arm phase-2 trials of patients with biochemical recurrence (prostate specific antigen [PSA] 0.4-3.0 ng/mL) and negative conventional imaging after radical prostatectomy and postoperative radiation therapy. All patients underwent [18F]DCFPyL positron emission tomography/computed tomography. Patients with molecularly defined oligorecurrent prostate cancer underwent MDT with stereotactic body radiation therapy or surgery, without androgen deprivation therapy (ADT). The primary end point was biochemical response (≥50% PSA decline from baseline). Secondary end points included PSA progression-free survival and ADT-free survival. The sample size of 37 MDT patients was determined based on a Simon's 2-stage design with biochemical response rate >20%, and this design was also applied for the subsequent independent validation cohort. RESULTS: Seventy-four patients underwent MDT: 37 each in the initial and validation cohorts. Both cohorts met the prespecified biochemical response rate and completed the planned 2-stages of accrual. For the pooled cohort, the median number of prostate specific membrane antigen positron emission tomography avid lesions was 2 and most (87%) recurrences were nodal. Sixty-four (87%) had stereotactic body radiation therapy and 10 (13%) had surgery. Median follow-up (interquartile range [IQR]) for the initial, validation and combined cohorts were 41 (35-46) months, 14 months (7-21), and 24 months (14-41), respectively. The biochemical response rates for the initial, validation and combined cohorts were 59%, 43%, and 51%, respectively. For the combined cohort, median biochemical progression-free survival was 21 months (95% confidence interval, 13-not reached), and median ADT-free survival was 45 months (95% confidence interval, 31-not reached). CONCLUSIONS: Half of patients treated with MDT for molecularly defined-only oligorecurrent prostate cancer exhibited a biochemical response. This study provides necessary and validated evidence to support randomized trials aiming to determine whether MDT (alone or with systemic therapy) can affect clinically meaningful end points.

Global patterns of non-Hodgkin lymphoma in 2020.

We evaluated the global patterns of non-Hodgkin lymphoma (NHL) in 2020 using the estimates of NHL incidence and mortality in 185 countries that are part of the GLOBOCAN 2020 database, developed by the International Agency for Research on Cancer (IARC). As well as new cases and deaths of NHL, corresponding age-standardized (world) rates (ASR) of incidence and mortality per 100 000 person-years were derived by country and world region. In 2020, an estimated 544 000 new cases of NHL were diagnosed worldwide, and approximately 260 000 people died from the disease. Eastern Asia accounted for a quarter (24.9%) of all cases, followed by Northern America (15.1%) and South-Central Asia (9.7%). Incidence rates were higher in men than in women, with similar geographical patterns. While the incidence rates were highest in Australia and New Zealand, Northern America, Northern Europe and Western Europe (>10/100 000 for both sexes combined), the highest mortality rates (>3/100 000) were found in regions in Africa, Western Asia and Oceania. The large variations and the disproportionately higher mortality in low- and middle-income countries can be related to the underlying prevalence and distribution of risk factors, and to the level of access to diagnostic and treatment facilities.

Priorities for cancer research in low- and middle-income countries: a global perspective.

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public.

Enhancing International Cancer Organization Collaborations: King Hussein Cancer Center and Princess Margaret Cancer Centre Model for Collaboration.

Collaborative partnerships, which link two health organizations with shared characteristics to achieve common goals and to improve healthcare quality, are becoming increasingly common in oncology. The purpose of this study is to review the collaboration between King Hussein Cancer Center (KHCC) and Princess Margaret Cancer Centre (PM). The context, input, process, and product (CIPP) model, a quasi-experimental form of program evaluation, has been applied to the KHCC-PM collaboration. This model is well suited to evaluate complex collaborations as it does not assume linear relationships. Data sources include stakeholders' judgements of the collaboration, assessment of achievements, and informal interviews with key participants involved in the program. KHCC and PM are recognized as high-caliber comprehensive cancer centers, with a common goal of delivering high-quality care to patients. Through personal relationships among faculty in the centers and the perceived opportunities for mutual benefit, KHCC and PM signed a memorandum of understanding in 2013 to enter into a formal partnership. This partnership has been an evolving process that started with collaboration on education and grew to include clinical care. Research is an area for potential future collaboration. Enabling factors in the collaboration include dedication of individuals involved, trusting relationships amongst faculty, and the reciprocal nature of the relationship. Challenges have been financial, competing interests, and the absence of a successful collaborative model to follow. The KHCC and PM collaboration has been successful. A strategic plan is being developed and followed to guide areas of expansion.

Examining the Landscape of Prognostic Factors and Clinical Outcomes for Cancer Control.

Prognostic factors have important utility in various aspects of cancer surveillance, including research, patient care, and cancer control programmes. Nevertheless, there is heterogeneity in the collection of prognostic factors and outcomes data globally. This study aimed to investigate perspectives on the utility and application of prognostic factors and clinical outcomes in cancer control programmes. A qualitative phenomenology approach using expert interviews was taken to derive a rich description of the current state and future outlook of cancer prognostic factors and clinical outcomes. Individuals with expertise in this work and from various regions and institutions were invited to take part in one-on-one semi-structured interviews. Four areas related to infrastructure and funding challenges were identified by participants, including (1) data collection and access; (2) variability in data reporting, coding, and definitions; (3) limited coordination among databases; and (4) conceptualization and prioritization of meaningful prognostic factors and outcomes. Two areas were identified regarding important future priorities for cancer control: (1) global investment and intention in cancer surveillance and (2) data governance and exchange globally. Participants emphasized the need for better global collection of prognostic factors and clinical outcomes data and support for standardized data collection and data exchange practices by cancer registries.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

Global Radiotherapy: Current Status and Future Directions-White Paper.

Recognizing the increase in cancer incidence globally and the need for effective cancer control interventions, several organizations, professional bodies, and international institutions have proposed strategies to improve treatment options and reduce mortality along with minimizing overall incidence. Despite these efforts, an estimated 9.6 million deaths in 2018 was attributed to this noncommunicable disease, making it the second leading cause of death worldwide. Left unchecked, this will further increase in scale, with an estimated 29.5 million new cases and 16.3 million deaths occurring worldwide in 2040. Although it is known and generally accepted that cancer services must include radiotherapy, such access is still very limited in many parts of the world, especially in low- and middle-income countries. After thorough review of the current status of radiotherapy including programs worldwide, as well as achievements and challenges at the global level, the International Atomic Energy Agency convened an international group of experts representing various radiation oncology societies to take a closer look into the current status of radiotherapy and provide a road map for future directions in this field. It was concluded that the plethora of global and regional initiatives would benefit further from the existence of a central framework, including an easily accessible repository through which better coordination can be done. Supporting this framework, a practical inventory of competencies needs to be made available on a global level emphasizing the knowledge, skills, and behavior required for a safe, sustainable, and professional practice for various settings. This white paper presents the current status of global radiotherapy and future directions for the community. It forms the basis for an action plan to be developed with professional societies worldwide.

Clinical integration of machine learning for curative-intent radiation treatment of patients with prostate cancer.

Machine learning (ML) holds great promise for impacting healthcare delivery; however, to date most methods are tested in 'simulated' environments that cannot recapitulate factors influencing real-world clinical practice. We prospectively deployed and evaluated a random forest algorithm for therapeutic curative-intent radiation therapy (RT) treatment planning for prostate cancer in a blinded, head-to-head study with full integration into the clinical workflow. ML- and human-generated RT treatment plans were directly compared in a retrospective simulation with retesting (n = 50) and a prospective clinical deployment (n = 50) phase. Consistently throughout the study phases, treating physicians assessed ML- and human-generated RT treatment plans in a blinded manner following a priori defined standardized criteria and peer review processes, with the selected RT plan in the prospective phase delivered for patient treatment. Overall, 89% of ML-generated RT plans were considered clinically acceptable and 72% were selected over human-generated RT plans in head-to-head comparisons. RT planning using ML reduced the median time required for the entire RT planning process by 60.1% (118 to 47 h). While ML RT plan acceptability remained stable between the simulation and deployment phases (92 versus 86%), the number of ML RT plans selected for treatment was significantly reduced (83 versus 61%, respectively). These findings highlight that retrospective or simulated evaluation of ML methods, even under expert blinded review, may not be representative of algorithm acceptance in a real-world clinical setting when patient care is at stake.

Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis.

BACKGROUND: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. OBJECTIVE: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). DESIGN/SETTING/PARTICIPANTS: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. INTERVENTIONS: All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. OUTCOME MEASUREMENTS/STATISTICAL ANALYSIS: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and ß of 0.1. RESULTS: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. CONCLUSIONS: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa. PATIENT SUMMARY: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.