Living with tuberculosis: a qualitative study of patients' experiences with disease and treatment.

BACKGROUND: Although tuberculosis (TB) is a curable disease, treatment is complex and prolonged, requiring considerable commitment from patients. This study aimed to understand the common perspectives of TB patients across Brazil, Russia, India, China, and South Africa throughout their disease journey, including the emotional, psychological, and practical challenges that patients and their families face. METHODS: This qualitative market research study was conducted between July 2020 and February 2021. Eight TB patients from each country (n = 40) completed health questionnaires, video/telephone interviews, and diaries regarding their experiences of TB. Additionally, 52 household members were interviewed. Patients at different stages of their TB treatment journey, from a range of socioeconomic groups, with or without TB risk factors were sought. Anonymized data underwent triangulation and thematic analysis by iterative coding of statements. RESULTS: The sample included 23 men and 17 women aged 13-60 years old, with risk factors for TB reported by 23/40 patients. Although patients were from different countries and cultural backgrounds, experiencing diverse health system contexts, five themes emerged as common across the sample. 1) Economic hardship from loss of income and medical/travel expenses. 2) Widespread stigma, delaying presentation and deeply affecting patients' emotional wellbeing. 3) TB and HIV co-infection was particularly challenging, but increased TB awareness and accelerated diagnosis. 4) Disruption to family life strained relationships and increased patients' feelings of isolation and loneliness. 5) The COVID-19 pandemic made it easier for TB patients to keep their condition private, but disrupted access to services. CONCLUSIONS: Despite disparate cultural, socio-economic, and systemic contexts across countries, TB patients experience common challenges. A robust examination of the needs of individual patients and their families is required to improve the patient experience, encourage adherence, and promote cure, given the limitations of current treatment.

Does a groin node dissection in vulvar cancer affect groin recurrence and overall survival?: Results from a population-based cohort study.

BACKGROUND: To determine, in a population-based cohort of vulvar cancer patients, if groin node dissection (GND) decreases the risk of groin recurrence and increases overall survival. METHODS: This population-based retrospective cohort study includes all cases of invasive squamous cell carcinoma identified in a provincial cancer registry from 1998 to 2007. Data collection was completed for all clinical and pathologic factors by chart abstraction. Cumulative incidence functions for recurrence were estimated, accounting for death before recurrence as a competing risk. Multivariable Cox regression models examined the associations between GND and groin recurrence, and overall survival. RESULTS: Clinical and pathologic data were collected for 1109 patients, of which 1038 patients were eligible for GND. 647 patients (62%) had a GND, while 391 patients (38%) did not. Median follow-up was 2.8years. Cumulative incidence plots demonstrate that the risk of death without recurrence was consistently higher than groin recurrence in each year after diagnosis. On multivariate analysis, GND was not significantly associated with decreased groin recurrence (HR 0.91, 95% CI 0.58-1.44, p=0.70). The hazard of death was 15% lower for women who received GND (HR 0.85, 95% CI 0.63-1.16, p=0.32), but this difference was not statistically significant. CONCLUSIONS: There was no significant difference in groin recurrence or overall survival in those with or without GND in this population-based cohort, raising questions whether a subgroup of patients may not benefit from GND. Patients had a higher probability of dying before groin recurrence could occur. Future trial design should consider death as a competing risk.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

OBJECTIVE: To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). METHODS: Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. RESULTS: 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). CONCLUSION: Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients.

Patient, tumor, and health system factors affecting groin node dissection rates in vulvar carcinoma: A population-based cohort study.

OBJECTIVE: To determine the rate of groin node dissection (GND) for invasive vulvar carcinoma in a population-based cohort, and the patient, tumor, or health system factors associated with having this procedure. METHODS: This retrospective population-based cohort includes all cases of invasive squamous cell carcinoma identified in the provincial cancer registry from 1998 to 2007. Chart abstraction was completed for all clinical and pathologic factors. Descriptive analyses with chi-squared tests were used for comparing proportions between patient groups. Multivariable logistic regression analysis was implemented to determine factors associated with having a GND. RESULTS: Data was collected for 1109 patients; 1038 patients were included in this analysis. 647 (62%) had a GND as part of primary management of their vulvar cancer, while 391 (38%) did not. When those with depth of invasion ≤1mm and no GND were removed, the GND rate increased to 68%. Reasons for no GND included age, obesity, advanced disease, or comorbidities. Factors significantly associated with omission of GND were increasing age (OR 0.98, CI 0.97-0.99), severe comorbidities (OR 0.57, CI 0.42-0.78), lower income quintile (OR 0.71, CI 0.54-0.95), and surgeon type (non-gynecologic oncologist vs gynecologic oncologist) (OR 0.43, CI 0.22-0.85), whereas depth of invasion >1mm was significantly associated with having a GND (OR 2.75, CI 2.08-3.62). CONCLUSION: This population-based cohort demonstrates 32% of invasive vulvar cancer patients did not have a GND at initial management. Vulvar cancer patients should be evaluated by clinicians with expertise in this rare disease to ensure that a GND is completed when feasible.

State of the science in cervical cancer: where we are today and where we need to go.

Invasive cervical cancer remains an important global cause of death, despite the declining prevalence within the United States. Definitive therapies, including surgical resection of early-stage disease and chemoradiation for locally advanced disease, can be curative. For women who experience local or distant recurrences, the prognosis remains poor and better treatments are required. On July 18, 2013, The Gynecologic Oncology Group sponsored a State of the Science in Cervical Cancer Symposium with experts, researchers, clinicians, and interested stakeholders. This article summarize the progress that has been made, questions that require further investigation, and contemporary genomic findings and innovative treatments that may help inform the next generation of clinical trials for patients with cervical cancer.

Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in gynecologic oncology group trials of cisplatin-based chemoradiation.

OBJECTIVE: Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer. METHODS: Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. RESULTS: Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies. CONCLUSION: Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation.

Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer.

OBJECTIVE: To prospectively define the prevalence of lymph node metastasis (LNM) in at risk endometrial cancer (EC). METHODS: From 2004 to 2008, frozen section based Mayo Criteria prospectively identified patients "not at-risk" of LNM (30% EC population; grade I/II, <50% myometrial invasion and tumor diameter ≤ 2 cm) where lymphadenectomy was not recommended. The remaining 70% EC cohort was considered "at-risk" of LNM; where a systematic pelvic and infrarenal paraaortic lymphadenectomy was recommended. Patients were prospectively followed. The area between renal vein and inferior mesenteric artery (IMA) was labeled as high paraaortic area. For calculating the prevalence of LNM in high paraaortic area, the denominator was the population with known anatomic location of nodal tissue in relation to the IMA. RESULTS: Of the 742 patients, 514 were at risk; of which 89% underwent recommended lymphadenectomy. A mean (± standard deviation) of 36 (± 14) pelvic and 18 (± 9) paraaortic nodes were harvested. The prevalence of pelvic and paraaortic LNM was 17% and 12%, respectively. In presence of pelvic LNM, 51% had paraaortic LNM. In absence of pelvic LNM, 3% had paraaortic LNM; of which 67% was located exclusively in high paraaortic area. Among patients with paraaortic LNM, 88% had high paraaortic LNM; and 35% had only high paraaortic LNM. The cases of paraaortic LNM with negative pelvic nodes seemed to cluster in moderate to high grade endometrioid EC with ≥ 50% myometrial invasion. CONCLUSION: We present reference data for the prevalence of LNM in at-risk EC patients to guide lymphadenectomy decisions for clinical and research purposes.

Radical surgery in patients with residual disease after (chemo)radiation for cervical cancer.

OBJECTIVE: The aim of this study was to determine possible impact of routinely scheduled biopsies and more radical surgery for residual central disease in locally advanced cervical cancer after (chemo)radiation. METHODS/MATERIALS: Data were analyzed of a consecutive series of cervical cancer patients (The International Federation of Gynecology and Obstetrics stages IB1-IVA) treated with (chemo) radiation between 1994 and 2011. Patients underwent gynecologic examination with biopsies 8 to 10 weeks after treatment. Since 2001, larger biopsies by electric loop excision were taken, and more radical surgery (type III hysterectomy or exenteration) was performed for central residual disease. Primary outcome was locoregional recurrence. Secondary outcomes were treatment-associated morbidity and disease-specific survival. RESULTS: Primary (chemo)radiation was given to 491 cervical cancer patients; 345 patients had a posttreatment biopsy. Viable tumor cells were identified in 84 patients, and 61 patients were eligible for salvage surgery. Residual disease after (chemo)radiation was an independent poor prognostic factor (hazard ratio, 3.59; 95% confidence interval, 2.18-5.93; P < 0.001). After 2001, larger biopsies were more frequently taken (29% vs 76%, P < 0.001), and in patients without viable tumor cells, locoregional recurrence after 2001 decreased from 21% to 10% (P = 0.01). After 2001, more patients underwent more radical surgery (46% vs 90%) (P < 0.001). Locoregional recurrence after surgery before 2001 occurred in 6 (46%) of the 13 patients, comparable with 19 (40%) of the 48 (P = 0.67) after 2001. More radical surgery was not associated with improved disease-specific survival (HR, 0.84; 95% CI, 0.20-3.46; P = 0.81) but did result in significantly more severe morbidity. CONCLUSION: More radical surgery in patients with (minimal) central residual disease identified by routine biopsy 8 to 10 weeks after (chemo)radiation does not improve survival and should not be recommended.

Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting: taking endometrial cancer trials into the translational era.

OBJECTIVE: The second Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting was held on December 1, 2012, and included international multidisciplinary representatives of the 24 member groups. The aims were to review recent advances in molecular pathology of endometrial cancer, focusing on molecular-based therapy, and to identify key hypotheses and issues to be addressed through international collaborative clinical trials. METHODS: Reviews and summaries of current knowledge were presented followed by parallel working group sessions for surgery, adjuvant and systemic therapy, and translational research. Plenary discussions were held to integrate translational and clinical issues, and a final discussion session to agree on key trial concepts. RESULTS AND CONCLUSIONS: Proposals to take forward on the following trials were agreed: (1) lymphadenectomy to direct adjuvant treatment in women with high-risk endometrial cancer, including a sentinel node substudy; (2) conservative therapy for low-risk endometrial cancers in morbidly obese women with high surgical risks and for fertility-sparing treatment in premenopausal patients; (3) adjuvant therapy for women with early-stage carcinosarcoma. A proposal was made that a GCIG Early Phase Consortium be developed to serve as an international platform for rapid assessment of biomarkers.

Vaginal vault dehiscence and increased use of vaginal vault brachytherapy: what are the implications?

Literature reports describe the potential for increased incidence of vaginal vault dehiscence after minimally invasive surgery, and incidental reports of vaginal vault dehiscence with vaginal vault brachytherapy. This review explores the risk of increased vaginal complications in a setting of greater use of both minimally invasive surgical techniques and adjuvant vaginal vault brachytherapy in early endometrial cancer. The impact of associated patient-related and tumor-related risk factors on clinical decision making is evaluated in selecting therapy that provides optimal tumor control while minimizing treatment adverse effects.

Role of molecular agents and targeted therapy in clinical trials for women with ovarian cancer.

There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.

Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials.

BACKGROUND: Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. METHODS: Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. FINDINGS: Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 for mortality during the active study period, and I(2) 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42). INTERPRETATION: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. FUNDING: German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).

Adenocarcinoma: a unique cervical cancer.

Adenocarcinoma of the cervix constitutes only approximately 20% of all cervical carcinomas; therefore, specific Level 1 evidence to guide patient management is lacking. Most trials have included this histologic subtype but in insufficient numbers to do more than generate hypotheses from subset analyses. As a consequence, our understanding of the natural history and optimal management of adenocarcinoma of the cervix is limited. The optimal management of adenocarcinoma of the cervix continues to be a subject of debate among practitioners as to whether or not it should be different from squamous cell carcinoma and what would constitute this management. The purpose of this review was to give an overview of the current knowledge on adenocarcinoma of the cervix and its differences from squamous cell carcinoma with regard to risk factors, prognosis, survival rates, patterns of recurrence, and response to treatment. This article will focus on possible specific therapeutic directions to explore in the management of locally advanced adenocarcinomas.

A phase II study of sunitinib in patients with locally advanced or metastatic cervical carcinoma: NCIC CTG Trial IND.184.

OBJECTIVE: Vascular endothethial growth factor (VEGF) and stem cell factor (c-KIT) signaling may play a role in the development and progression of cervical carcinoma. Sunitinib malate is an oral, multi-targeted tyrosine kinase inhibitor that inhibits receptors for VEGF, c-Kit and platelet-derived growth factor. This multi-centre phase II study was performed to evaluate the activity of sunitinib in women with locally advanced or metastatic cervical carcinoma who had received up to one prior line of chemotherapy for advanced disease. METHODS: Sunitinib, 50 mg/day, was administered in 6-week cycles (4 weeks on followed by 2 weeks off treatment). The primary endpoint was the objective response rate. RESULTS: Sixteen (84%) of 19 patients enrolled had stable disease (median duration 4.4 months, 2.3-17 months), but no objective response was observed. Median time to progression was 3.5 months (range, 2.7-7.0 months). Four patients had fistulae develop on study treatment and an additional patient developed a fistula 3.5 months after discontinuation of therapy. All five patients had received either prior chemoradiation or radiation. CONCLUSIONS: A higher rate of fistula formation (26.3%) was observed than would be expected and is of concern. Sunitinib has insufficient activity as a single agent in cervical cancer to warrant further investigation.

A role for adjuvant radiation in clinically early carcinoma of the endometrium?

Whereas radiation is recognized as a highly effective treatment modality in endometrial cancer, its role as adjuvant treatment after surgery in clinically early disease is declining. Randomized trials of both pelvic external beam radiation and vaginal vault brachytherapy have been conducted to evaluate their respective contribution. These trials have demonstrated that external beam radiation may decrease pelvic relapse rates compared with observation alone in high intermediate-risk groups, but this does not improve survival. Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) Study 2 confirmed that vaginal vault brachytherapy was equivalent to external beam radiation in preventing vaginal relapse. However, given the high rate of salvage of patients who develop vaginal recurrence and the significant risk of death from comorbidities, questions arise as to the relative merit of administering adjuvant radiation for all compared with a strategy of observation after surgery with treatment only for the 10% who have a relapse.The contribution of adjuvant radiation for high-risk disease, including those with grade III tumors with deep myometrial penetration, however, remains to be determined in ongoing trials.

The development of priority cervical cancer trials: a Gynecologic Cancer InterGroup report.

Since the late 1990s, when a spate of US studies reported the benefit of chemoradiation for cervical cancer, there has been a dearth of clinical trials in cervical cancer. This requires to be addressed with urgency because this disease is responsible for a quarter of a million deaths globally each year, mostly in developing countries, but therapeutic advances are required in all health care settings. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaborative of leading national groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representations from most of the GCIG groups and selected large centers in low- and middle-income countries. The focus was to identify consensus on several concepts for clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps most needing new evidence. The second half of the meeting was concerned with achieving consensus on the way forward. There were 2 principal outcomes. The first was a proposal to establish, under the umbrella of GCIG, a cervical cancer trials network of centers from countries currently outside GCIG (Eastern Europe, India, Thailand, Southern Africa, and South and Central America), which could increase international participation in trials, conducted within the principles of good clinical practice. The second was to identify the priorities for clinical trials. These included additional systemic therapy before or after chemoradiation; less radical surgery for small, early-stage tumors; the use of fewer fractions to improve cost-effectiveness of treatment in centers with limited resources; and chemotherapy to improve resectability of bulky tumors.

Patient outcome study of concurrent chemoradiation, external beam radiotherapy, and high-dose rate brachytherapy in locally advanced carcinoma of the cervix.

INTRODUCTION: A regimen of concurrent chemoradiation for definitive treatment of cervical cancer is widely used. This retrospective review has been conducted to determine the outcomes and late toxic effect associated with the specific regimen of whole-pelvic external beam radiotherapy of 45 Gy in 25 fractions with parametrial boosts of 5.4 or 9 Gy and HDR brachytherapy (BT) of 30 Gy in 5 fractions to point A delivered by tandem and ring. This protocol is accepted by the Gynecological Oncology Group and endorsed by the American Brachytherapy Society, but no late toxic effect data have been reported. MATERIALS AND METHODS: The electronic records of sequential patients treated definitively at the Sunnybrook Odette Cancer Centre between January 2006 and December 2008 were reviewed. Patient-, tumor-, and treatment-related details (including external beam radiotherapy, BT, and chemotherapy) were obtained. Outcome measures included disease-free status, dates and sites of first recurrence, survival, and grade 3/4 late toxic effect results (Common Terminology Criteria Adverse Events 3.0 criteria). Exclusion criteria were no follow-up or a planned alternative regimen. RESULTS: One hundred twenty-two patients (+11 excluded) were treated with a median follow-up of 18 months from diagnosis. The actuarial 2-year disease-free survival rate was 70%. The median time to recurrence was 8 months (range, 2-22 months). The median time to toxic effect was 10 months (range 4-27 months). Grade 3/4 toxic effect was observed in 13 patients (11%). The actuarial grade 3/4 toxic effect rate at 2 years was 14%. CONCLUSIONS: Despite a relatively short follow-up, the toxicity of this regimen seems high compared with other retrospective series, although pelvic control is good. Consideration should be given to a reduction in BT dose alternatively when feasible image-guided BT may allow maintenance of tumor dose with reduced dose to organs at risk.

Current academic clinical trials in ovarian cancer: Gynecologic Cancer Intergroup and US National Cancer Institute Clinical Trials Planning Meeting, May 2009.

OBJECTIVE: To review the current status of large phase academic clinical trials for women with ovarian cancer, address cross-cutting issues, and identify promising areas for future collaboration. METHODS: In May 2009, the Gynecologic Cancer Intergroup, which represents 19 Cooperative Groups conducting trials for women with gynecologic cancer, and the US National Cancer Institute convened a Clinical Trials Planning Meeting. RESULTS: The topics covered included the impact of new developments in cancer biology upon molecular targets and novel agents, pharmacogenomics, advances in imaging, the potential benefit of diet and exercise to reduce the risk of recurrence, academic partnership with industry, statistical considerations for phases 2 and 3 trials, trial end points, and symptom benefit and health-related quality-of-life issues. The clinical trials discussed spanned the spectrum of ovarian cancer from initial diagnosis, staging, and cytoreductive surgery to consolidation chemotherapy, and treatment of recurrent disease. CONCLUSIONS: Ongoing and effective collaboration with industry, government, and patients aims to ensure that the most important scientific questions can be answered rapidly. We encourage women with ovarian cancer and their oncologists to consider participation in the academic clinical trials conducted by the member groups of the Gynecologic Cancer Intergroup.

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report.

BACKGROUND: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. METHODS: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. CONCLUSIONS: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology.