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After a median of nearly 4 years of follow-up, the use of radiotherapy combined with chemotherapy in patients with stage III or IVA endometrial carcinoma was not associated with longer relapse-free survival than the use of chemotherapy alone.

[...]with the rate of endometrial cancer on the rise, clinicians will find more patients with recurrent endometrial cancer in their practice. 2 Furthermore, the publication of Gynecologic Oncology Group 258 (GOG 258), which did not show improvement in relapse-free survival with chemoradiotherapy compared with chemotherapy alone, resulted in reduced use of pelvic radiation for advanced endometrial cancer despite higher rates of local recurrences seen with the omission of radiation therapy.2 Current imaging recommendations Following definitive oncologic therapy, patients are followed closely by both gynecologic and radiation oncologists with history and physical exam, as approximately 25–30% are at risk of developing disease recurrence and metastasis. 3 4 NCCN guidelines recommend that endometrial cancer patients are followed every 3 to 6 months for the first 2 to 3 years after treatment, every 6 months for years 4 and 5, and then on a yearly basis.4 NCCN notes that surveillance imaging is not indicated unless there is clinical suspicion of recurrent or metastatic disease. In GOG 249, which randomized stage I/II endometrial cancer patients to receive either adjuvant carboplatin/paclitaxel chemotherapy and vaginal cuff brachytherapy or adjuvant pelvic radiation, patients were followed with abdominopelvic imaging (CT or MRI) and chest X-ray within 4 weeks after study therapy, every 6 months for 2 years, then annually for 3 years. 6 GOG 258, which randomized stage III-IVA patients to receive either chemoradiation or chemotherapy alone, evaluated patients with CT of the abdomen and pelvis and chest radiography at baseline, at the end of treatment, every 6 months for the first 2 years, and then annually up to 5 years.2 Salvage of asymptomatic recurrences While 95% of patients present with early-stage endometrial cancer, women who develop recurrent or metastatic disease will find their treatment options limited and survival poor. 1 Even though vaginal recurrences can be detected clinically, regional nodal and distant recurrences are difficult to assess without imaging. With the publication of GOG 258, there may have been a decline in the use of pelvic irradiation for locally advanced endometrial cancer, as no improvement in relapse-free survival was seen with the addition of radiation to chemotherapy. 2 In this study, women who did not receive radiation therapy experienced a higher nodal recurrence rate than those who did (20% vs 11%, respectively). [...]in GOG 249, the omission of pelvic radiation in favor of chemotherapy and vaginal cuff brachytherapy similarly resulted in a higher regional nodal recurrence rate of 9% versus 4%, respectively. 6 As noted above, both studies integrated surveillance imaging into patient follow-up.

Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15–27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0–277). 5-year crude disease-free survival was 83·3% (95% CI 78·8–87·0) for patients with pCR (61/419 patients had disease recurrence) and 65·6% (63·6–68·0) for those without pCR (747/2263; HR 0·44, 95% CI 0·34–0·57; p<0·0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0·54 (95% CI 0·40–0·73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0·91 (95% CI 0·73–1·12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. None.

Since the National Cancer Institute (NCI) alert of concurrent chemoradiotherapy, radiotherapy has been changed from external beam radiotherapy plus brachytherapy to platinum-based concurrent chemoradiotherapy. Therefore, concurrent chemoradiotherapy plus brachytherapy has become a standard treatment for locally advanced cervical cancer. Simultaneously, definitive radiotherapy has been changed gradually from external beam radiotherapy plus low-dose-rate intracavitary brachytherapy to external beam radiotherapy plus high-dose-rate intracavitary brachytherapy. Cervix cancer is uncommon in developed countries; hence, international collaborations have been critical in large-scale clinical trials. The Cervical Cancer Research Network (CCRN), created from the Gynecologic Cancer InterGroup (GCIG), has investigated various concurrent chemotherapy regimens and sequential methods of radiation and chemotherapy. Most recently, many clinical trials of combining immune checkpoint inhibitors with radiotherapy have been ongoing for sequential or concurrent settings. During the last decade, the method of standard radiation therapy has changed from three-dimensional conformal radiation therapy to intensity-modulated radiation therapy for external beam radiotherapy and from two-dimensional to three-dimensional image-guided approaches for brachytherapy. Recent improvements include stereotactic ablative body radiotherapy and MRI-guided linear accelerator (MRI-LINAC) using adaptive radiotherapy. Here we review the current progress of radiation therapy during the last two decades.

In the modern era, cervical cancer treatment has become more multidisciplinary in nature. Accurate and precise staging based on clinical and radiographic findings, as well as identification of pathologic and molecular risk factors, may alter treatment recommendations. Additionally, the body of evidence guiding optimal treatment recommendations continues to grow. Multiple specialists including gynecologic oncologists, radiation oncologists, medical oncologists, radiologists, pathologists, and other ancillary staff, often with subspecialty experience in gynecology or cancer care, now staff multidisciplinary gynecologic oncology teams. This review highlights the basis of multidisciplinary treatment of early-stage cervical cancer, with a focus on surgical interventions, the role of adjuvant therapy, and indications for definitive chemoradiation. We specifically focus on the treatment of cervical cancer from stage IA1 (microinvasive disease) to stage IIB (parametrial involvement without involvement of pelvic sidewall). The staging manuals referenced in this review include the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging as well as the updated American Joint Committee on Cancer (AJCC) 9th edition (2021).

BackgroundIntraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in “real-world” clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment.MethodsTARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR).ResultsThe evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%.ConclusionThe local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Cervical cancer is the third most common cancer among women worldwide, with a disproportionately high burden of disease in less-developed regions of the world. The Cervix Cancer Research Network was founded by the Gynecologic Cancer InterGroup with a mission to improve outcomes in cervical cancer by enhancing international access to clinical trials, specifically in under-represented, underdeveloped areas. The Cervix Cancer Research Network held its third international educational symposium in Bucharest in 2018 and is the subject of this report. The purpose of this symposium was to advance the international understanding of cervical cancer treatment patterns, to foster recruitment to Cervix Cancer Research Network clinical trials, and identify key Cervix Cancer Research Network clinical trial concepts to improve cervical cancer care worldwide.

Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0–2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0–50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI –6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3–4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. National Health and Medical Research Council and National Cancer Institute.

Background Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed. Methods Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity. Results Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1–14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration. Conclusions The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).