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BACKGROUND:There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS:Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation–mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS:The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS:The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

There are currently no standard first-line treatment options for patients with higher grade 2–3, well-differentiated, advanced, gastroenteropancreatic neuroendocrine tumours. We aimed to investigate the efficacy and safety of first-line [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) treatment. NETTER-2 was an open-label, randomised, parallel-group, superiority, phase 3 trial. We enrolled patients (aged ≥15 years) with newly diagnosed higher grade 2 (Ki67 ≥10% and ≤20%) and grade 3 (Ki67 >20% and ≤55%), somatostatin receptor-positive (in all target lesions), advanced gastroenteropancreatic neuroendocrine tumours from 45 centres across nine countries in North America, Europe, and Asia. We used interactive response technologies to randomly assign (2:1) patients to receive four cycles (cycle interval was 8 weeks ± 1 week) of intravenous 177Lu-Dotatate plus intramuscular octreotide 30 mg long-acting repeatable (LAR) then octreotide 30 mg LAR every 4 weeks (177Lu-Dotatate group) or high-dose octreotide 60 mg LAR every 4 weeks (control group), stratified by neuroendocrine tumour grade (2 vs 3) and origin (pancreas vs other). Tumour assessments were done at baseline, week 16, and week 24, and then every 12 weeks until disease progression or death. The primary endpoint was progression-free survival by blinded, independent, central radiology assessment. We did the primary analysis at 101 progression-free survival events as the final progression-free survival analysis. NETTER-2 is registered with ClinicalTrials.gov, NCT03972488, and is active and not recruiting. Between Jan 22, 2020, and Oct 13, 2022, we screened 261 patients, 35 (13%) of whom were excluded. We randomly assigned 226 (87%) patients (121 [54%] male and 105 [46%] female) to the 177Lu-Dotatate group (n=151 [67%]) and control group (n=75 [33%]). Median progression-free survival was 8·5 months (95% CI 7·7–13·8) in the control group and 22·8 months (19·4–not estimated) in the 177Lu-Dotatate group (stratified hazard ratio 0·276 [0·182–0·418]; p<0·0001). During the treatment period, adverse events (of any grade) occurred in 136 (93%) of 147 treated patients in the 177Lu-Dotatate group and 69 (95%) of 73 treated patients in the control group. There were no study drug-related deaths during the treatment period. First-line 177Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumours. 177Lu-Dotatate should be considered a new standard of care in first-line therapy in this population. Advanced Accelerator Applications, a Novartis Company.

Background: Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC. Methods: Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined. Results: In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65–14.32) and PFS 6.1 months (95% CI 5.19–8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0–23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia ( P <0.0001), vomiting ( P <0.001) and fatigue ( P =0.01) were significantly decreased. [ 18 F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS. Conclusions: In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.

Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic. Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049). Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status. National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).

Background The current treatment of ovarian cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second- or third-line systemic chemotherapy afterward. Methods In an 8-year period (2006–2013), 120 women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] III c and IV) who experienced disease recurrence after initial treatment with conservative or debulking surgery and systemic chemotherapy were randomized into two groups. Group A comprised 60 patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group B comprised 60 patients treated with CRS only and systemic chemotherapy. Results The mean survival for group A was 26.7 versus 13.4 months in group B ( p  < 0.006). Three-year survival was 75 % for group A versus 18 % for group B ( p  < 0.01). In the HIPEC group, the mean survival was not different between patients with platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8 months). On the other hand, in the non-HIPEC group, there was a statistically significant difference between platinum-sensitive versus platinum-resistant disease (15.2 vs. 10.2 months, p  < 0.002). Complete cytoreduction was associated with longer survival. Patients with a peritoneal cancer index score of <15 appeared also to have longer survival. Conclusions The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with recurrence in an initially advanced ovarian cancer.

The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival. This randomised controlled trial was done at 85 centres in Japan. Patients with stage II–IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m2 on day 1) or dose-dense treatment (carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m2 on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratified by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915. 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9–85·6). Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3–33·8] vs 17·5 months [15·7–21·7]; hazard ratio [HR] 0·76, 95% CI 0·62–0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2–∞) in the dose-dense treatment group and 62·2 months (52·1–82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63–0·99; p=0·039). Dose-dense treatment offers better survival than conventional treatment and is a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer. Japanese Gynecologic Oncology Group, Bristol-Myers Squibb.

Poor prognosis germ-cell tumours are only cured in about half of patients. We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with germ-cell tumours. In this phase 3, multicentre, randomised trial, patients were enrolled from France (20 centres), USA (one centre), and Slovakia (one centre). Patients were eligible if they were older than 16 years, had evidence of testicular, retroperitoneal, or mediastinal non-seminomatous germ cell tumours based on histological findings or clinical evidence and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor prognosis criteria. After one cycle of BEP (intravenous cisplatin [20 mg/m2 per day for 5 days], etoposide [100 mg/m2 per day for 5 days], and intramuscular or intravenous bleomycin [30 mg per day on days 1, 8, and 15]), patients' human chorionic gonadotropin and alfa-fetoprotein concentrations were measured at day 18–21. Patients with a favourable decline in human chorionic gonadotropin and alfa-fetoprotein continued BEP (Fav-BEP group) for 3 additonal cycles, whereas patients with an unfavourable decline were randomly assigned (1:1) to receive either BEP (Unfav-BEP group) or a dose-dense regimen (Unfav-dose-dense group), consisting of intravenous paclitaxel (175 mg/m2 over 3 h on day 1) before BEP plus intravenous oxaliplatin (130 mg/m2 over 3 h on day 10; two cycles), followed by intravenous cisplatin (100 mg/m2 over 2 h on day 1), intravenous ifosfamide (2 g/m2 over 3 h on days 10, 12, and 14), plus mesna (500 mg/m2 at 0, 3, 7 and 11 h), and bleomycin (25 units per day, by continuous infusion for 5 days on days 10–14; two cycles), with granulocyte-colony stimulating factor (lenograstim) support. Centrally blocked computer-generated randomisation stratified by centre was used. The primary endpoint was progression-free survival and the efficacy analysis was done in the intention-to-treat population. The planned trial accrual was completed in May, 2012, and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00104676. Between Nov 28, 2003, and May 16, 2012, 263 patients were enrolled and 254 were available for tumour marker assessment. Of these 51 (20%) had a favourable marker assessment, and 203 (80%) had an unfavourable tumour marker decline; 105 were randomly assigned to the Unfav-dose-dense group and 98 to the Unfav-BEP group. 3-year progression-free survival was 59% (95% CI 49–68) in the Unfav-dose-dense group versus 48% (38–59) in the Unfav-BEP group (HR 0·66, 95% CI 0·44–1·00, p=0·05). 3-year progression-free survival was 70% (95% CI 57–81) in the Fav-BEP group (HR 0·66, 95% CI 0·49–0·88, p=0·01 for progression-free survival compared with the Unfav-BEP group). More grade 3–4 neurotoxic events (seven [7%] vs one [1%]) and haematotoxic events occurred in the Unfav-dose-dense group compared with in the Unfav-BEP group; there was no difference in grade 1–2 febrile neutropenia (18 [17%] vs 18 [18%]) or toxic deaths (one [1%] in both groups). Salvage high-dose chemotherapy plus a stem-cell transplant was required in six (6%) patients in the Unfav-dose-dense group and 16 (16%) in the Unfav-BEP group. Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline. Institut National du Cancer (Programme Hospitalier de Recherche Clinique).

The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care.

Patients who complete neoadjuvant chemotherapy for breast cancer without a pathological complete response have a high risk of relapse. A randomized trial comparing capecitabine with no additional adjuvant therapy showed that capecitabine prolonged disease-free and overall survival. Patients who have residual invasive breast cancer after the receipt of neoadjuvant chemotherapy have a high risk of relapse. 1 The rate of complete response as assessed on pathological testing (hereafter, pathological complete response) ranges from 13 to 22% among patients with human epidermal growth factor receptor 2 (HER2)–negative primary breast cancer. 1 Patients who do not have a pathological complete response after the receipt of neoadjuvant taxane and anthracycline chemotherapy have a 20 to 30% risk of relapse. 2 Patients with HER2-negative cancer who receive neoadjuvant chemotherapy often receive postoperative radiation therapy, whereas endocrine therapy is administered to patients with hormone-receptor–positive disease . . .

Background: Stage at diagnosis is a key predictor of overall cancer outcome. For the first time, stage completeness is high enough for robust analysis for the whole of England. Methods: We analysed data from the National Cancer Registration Service’s (NCRS) Cancer Analysis System on persons diagnosed with breast, colorectal, lung, prostate or ovarian cancers in England in 2012. One-year relative survival (followed-up to the end of 2013) was calculated along with adjusted excess rate ratios, for mortality within 1 year. Results: One-year relative survival decreased with increasing stage at diagnosis. For breast, prostate and colorectal cancers survival showed a major reduction for stage 4 cancers, whereas for lung and ovarian cancers there were substantial decreases in relative survival for each level of increase in stage. Excess rate ratios for mortality within 1 year of diagnosis showed that stage and age were the most important cofactors, but they also identified the statistically significant effects of sex, income deprivation and geographic area of residence. Conclusions: Further reductions in mortality may be most effectively achieved by diagnosing all cancers before they progress to stage 4, but for lung and ovarian cancers there is also a need for a stage shift to earlier stages together with efforts to improve stage-specific survival at all stages.