Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of ...perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov , number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% 95·66% CI 21·3–35·5 to 35·4% 28·1–42·7; HR 0·79 0·62–1·02; p=0·058) in randomised patients; 8·1% (from 28·1% 21·2–36·6 to 36·2% 28·7–43·8; HR 0·77 0·60–1·00; p=0·041) in eligible patients; and 9·2% (from 33·2% 25·3–41·2 to 42·4% 34·0–50·5; HR 0·73 0·55–0·97; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 25% vs 27/170 16%; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
Summary Background Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free ...survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. Methods This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18–80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m2 , folinic acid 200 mg/m2 (DL form) or 100 mg/m2 (L form) on days 1–2 plus bolus, and fluorouracil 400 mg/m2 (bolus) and 600 mg/m2 (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. This trial is registered with ClinicalTrials.gov , number NCT00006479. Findings Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8·5 years (IQR 7·6–9·5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0·88, 95% CI 0·68–1·14; p=0·34). In all randomly assigned patients, median overall survival was 61·3 months (95% CI 51·0–83·4) in the perioperative chemotherapy group and 54·3 months (41·9–79·4) in the surgery alone group. 5-year overall survival was 51·2% (95% CI 43·6–58·3) in the perioperative chemotherapy group versus 47·8% (40·3–55·0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. Interpretation We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients. Funding Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, US National Cancer Institute, Sanofi-Aventis.
Although T-cell checkpoint blockade has revolutionized melanoma therapy, metastatic melanoma in pregnancy remains a challenging area of unmet need. Treatment with anti-PD1 therapy decreases ...foetal-maternal tolerance and increases the risk of pregnancy loss in animal studies and is considered category D by the Food and Drug Administration. We describe a unique case of conception and pregnancy, with successful maternal and foetal outcomes, in a patient with metastatic melanoma who had received combination anti-CTLA-4 and anti-PD1 therapy. A 32-year-old G0P0 lady, with a 10-year history of infertility of unclear cause, was found to be 7 weeks pregnant after 14 months of nivolumab maintenance therapy, having previously received combination ipilimumab and nivolumab. Nivolumab was ceased upon discovery of pregnancy in the first trimester. The patient had an uneventful pregnancy, followed by spontaneously premature labour, and delivered by caesarean section at 33 weeks' gestation. The foetus had moderate intrauterine growth restriction, as well as congenital hypothyroidism, which possibly constitutes the first documented case of foetal immune-related adverse event from maternal anti-PD1 exposure. No adverse events were noted in the mother. At 6 months of follow-up postpartum, the mother had a sustained complete response to treatment, and the baby had appropriate weight gain with normal developmental milestones. We summarize and discuss the available literature of immune checkpoint inhibitor exposure in pregnancy, which consists of a total of three case reports.
Purpose
Using population-based data for women diagnosed with stage I-III breast cancer, our aim was to examine the impact of time to treatment completion on survival and to identify factors ...associated with treatment delay.
Methods
This retrospective study used clinical and treatment data from the Queensland Oncology Repository. Time from diagnosis to completing surgery, chemotherapy and radiation therapy identified a cut-off of 37 weeks as the optimal threshold for completing treatment. Logistic regression was used to identify factors associated with the likelihood of completing treatment > 37 weeks. Overall (OS) and breast cancer-specific survival (BCSS) were examined using Cox proportional hazards models.
Results
Of 8279 women with stage I-III breast cancer, 31.9% completed treatment > 37 weeks. Apart from several clinical factors, being Indigenous (
p
= 0.002), living in a disadvantaged area (
p
= 0.003) and receiving ≥ two treatment modalities within the public sector (
p
< 0.001) were associated with an increased likelihood of completing treatment > 37 weeks. The risk of death from any cause was about 40% higher for women whose treatment went beyond 37 weeks (HR 1.37, 95%CI 1.16–1.61), a similar result was observed for BCSS. Using the surgery + chemotherapy + radiation pathway, a delay of > 6.9 weeks from surgery to starting chemotherapy was significantly associated with poorer survival (
p
= 0.001).
Conclusions
Several sociodemographic and system-related factors were associated with a greater likelihood of treatment completion > 37 weeks. We are proposing a key performance indicator for the management of early breast cancer where a facility should have > 90% of patients with a time from surgery to adjuvant chemotherapy < 6.9 weeks.
Abstract Introduction Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. ...There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction. Methods Patients were randomised to receive preoperative CT with cisplatin (80 mg/m2 ) and infusional 5 fluorouracil (1000 mg/m2 /d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m2 /d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life. Results Seventy-five patients were enroled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively ( p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT ( p = 0.83). Conclusions Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.
Purpose
The purpose of the present study is to explore the role of the general practitioners, family physicians and primary care physicians (GP) in the provision of follow-up cancer care.
Methods
...PubMed, MEDLINE and CINAHL were systematically searched for primary research focussing on the role of the GP from the perspective of GPs and patients. Data were extracted using a standardised form and synthesised using a qualitative descriptive approach.
Results
The initial search generated 6487 articles: 25 quantitative and 33 qualitative articles were included. Articles focused on patients’ and GPs’ perspectives of the GP role in follow-up cancer care. Some studies reported on the current role of the GP, barriers and enablers to GP involvement from the perspective of the GP and suggestions for future GP roles. Variations in guidelines and practice of follow-up cancer care in the primary health care sector exist. However, GPs and patients across the included studies supported a greater GP role in follow-up cancer care. This included greater support for care coordination, screening, diagnosis and management of physical and psychological effects of cancer and its treatment, symptom and pain relief, health promotion, palliative care and continuing normal general health care provision.
Conclusion
While there are variations in guidelines and practice of follow-up cancer care in the primary health care sector, GPs and patients across the reviewed studies supported a greater role by the GP.
Implications for Cancer Survivors
Greater GP role in cancer care could improve the quality of patient care for cancer survivors. Better communication between the tertiary sector and GP across the cancer phases would enable clear delineation of roles.
In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer ...(CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS.
The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models.
After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio HR = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98).
Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic lesions.ClinicalTrials.gov number NCT00006479.
Background
The optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) ...and neoadjuvant chemoradiotherapy (nCRT) for EAC.
Methods
Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000‐2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in‐hospital mortality, pathological outcomes, and survival rates were compared.
Results
Of the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in‐hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5‐year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found.
Conclusion
In this study no differences between nCT and nCRT were seen in postoperative complications and in‐hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.
BACKGROUNDDisparity in outcomes between Indigenous and non-Indigenous people after cancer diagnosis is multifactorial, including lower cancer screening participation, later diagnosis, reduced access ...and uptake of cancer treatment, higher rate of comorbidities, and barriers accessing the health system. Little is known about cancer survivorship experiences.
OBJECTIVEThe aim of this study was to explore Indigenous Australian cancer survivorʼs perspectives of cancer survivorship.
METHODSIndigenous people who completed cancer treatment 6 months to 5 years before fieldwork were recruited from a tertiary hospital and remote primary health service for this qualitative study. Data collection was guided by yarning methods, a culturally appropriate method emphasizing storytelling. Data were interpreted using a social constructionist framework.
RESULTSThirteen women and 6 men were interviewed. Participantsʼ past experiences contributed to their specific identity as survivors. Participants described factors affecting a positive transition from cancer patient to cancer survivor and the importance of ongoing family support in helping to manage survivorship. Finally, participants described a range of community support they received and provided to others and how this improved their cancer survivorship.
CONCLUSIONAlthough a range of experiences are presented, this study provides evidence that the survivorship perspectives of Indigenous cancer survivors may be, in part, shared by non-Indigenous cancer survivors.
IMPLICATIONS FOR PRACTICEAcknowledging Indigenous cancer survivorsʼ past experiences and how these influence their overall well-being is important for providing patient-centered and culturally appropriate care. Nurses and other healthcare professionals may use this knowledge to foster a range of coping strategies to assist Indigenous cancer survivors to live well.
To determine current and projected supply, demand and shortfall of medical oncologists (MOs) and the Australian chemotherapy utilisation rate.
A 2009 cross-sectional observational study of Australian ...adult medical oncology practice work patterns.
Electronic or paper self-administered questionnaire.
The 2009 and projected (2014) supply, demand and shortfall of full-time equivalent (FTE) MOs, and the chemotherapy utilisation rate.
476 medical oncology positions comprising 234 FTE MOs were identified. Of the 150 medical oncology practices, 117 (78%) were in metropolitan locations and 33 (22%) were in rural locations. The average number of new patients seen per FTE MO was 270 patients (ranging by state from 191 to 343). The demand for FTE MOs was estimated at 326 to 391 in 2009 and 361 to 432 in 2014. The shortfall of FTE MOs was estimated at 92 to 157 in 2009 and 84 to 156 in 2014. The chemotherapy utilisation rate was 19%.
The current shortage of MOs is expected to persist in the future. National strategies are needed to increase the capacity of the medical oncology workforce and the chemotherapy utilisation rate.
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