Compliance with recommended cancer patient pathway timeframes and choice of treatment differed by cancer type and place of residence among cancer patients in Norway in 2015-2016.

BACKGROUND: Cancer patient pathways (CPPs) were implemented in Norway to reduce unnecessary waiting times, regional variations, and to increase the predictability of cancer care for the patients. This study aimed to determine if 70% of cancer patients started treatment within the recommended time frames, and to identify potential delays. METHODS: Patients registered with a colorectal, lung, breast, or prostate cancer diagnosis at the Cancer Registry of Norway in 2015-2016 were linked with the Norwegian Patient Registry and Statistics Norway. Adjusting for sociodemographic variables, multivariable quantile (median) regressions were used to examine the association between place of residence and median time to start of examination, treatment decision, and start of treatment. RESULTS: The study included 20 668 patients. The proportions of patients who went through the CPP within the recommended time frames were highest among colon (84%) and breast (76%) cancer patients who underwent surgery and lung cancer patients who started systemic anticancer treatment (76%), and lowest for prostate cancer patients who underwent surgery (43%). The time from treatment decision to start of treatment was the main source of delay for all cancers. Travelling outside the resident health trust prolonged waiting time and was associated with a reduced odds of receiving surgery and radiotherapy for lung and rectal cancer patients, respectively. CONCLUSIONS: Achievement of national recommendations of the CCP times differed by cancer type and treatment. Identified bottlenecks in the pathway should be targeted to decrease waiting times. Further, CPP guidelines should be re-examined to determine their ongoing relevance.

Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer.

BACKGROUND: The incidence of colorectal cancer (CRC) in individuals of fertile age is increasing. Oxaliplatin is a cornerstone treatment in the adjuvant setting for stage III and high-risk stage II CRC. Limited data exist on possible side effects of oxaliplatin on fertility and gonadal function. More data is needed to guide possible fertility preservation procedures and aid evidence-based fertility counselling. PATIENTS AND METHODS: The aim of this study (EudraCT2006-002832-10) was to prospectively investigate sex hormones and sperm parameters after oxaliplatin-based adjuvant chemotherapy to clarify the risk of infertility and hypogonadism. Twenty males aged ≤55 years and 16 females aged ≤40 years were recruited from five hospitals in the Nordic countries. All had undergone radical surgery due to CRC and were given adjuvant oxaliplatin in combination with 5-fluorouracil. Measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and semen analysis were done in males, while LH, FSH and oestradiol were measured in females. Measurements were done prior to chemotherapy, after completion of adjuvant treatment and at follow-up 1 and up to 5 years after end of treatment. RESULTS: FSH and testosterone levels increased in males after chemotherapy treatment but were restored at follow-up. No patients developed hypogonadism. There was a trend towards a decrease in sperm concentration during treatment (p = 0.063). When comparing sperm concentration and rapid progressive motility of sperms prior to chemotherapy and at follow-up, there were no differences, and no patients became permanently azoospermic by treatment. No distinct altering of gonadal function could be observed in females. CONCLUSIONS: Oxaliplatin in combination with 5-fluorouracil seems to induce transient decrease in sperm concentration with recovery and a minor transient increase in FSH in males. No distinct altering of gonadal function was observed in females. The risk of infertility and hypogonadism in males and females after adjuvant oxaliplatin-based chemotherapy seems low.

Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer.

BACKGROUND: 5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination. METHODS AND MATERIALS: Patients with locally advanced anal cancer, T2 (≥4 cm)-4N0-3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule. RESULTS: Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46-70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3-4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%. CONCLUSION: The MTDs were determined as 5FU 800 mg/m(2) on RT days 1-4 and 29-32 and MMC 8 mg/m(2) on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.

Anticipating the clinical use of prognostic gene expression-based tests for colon cancer stage II and III: is Godot finally arriving?

PURPOSE: According to current recommendations for adjuvant treatment, patients with colon cancer stage II are not routinely offered chemotherapy, unless considered to have a high risk of relapse based on specific clinicopathological parameters. Following these criteria, it is challenging to identify the subgroup of patients that will benefit the most from adjuvant treatment. Contrarily, patients with colon cancer stage III are routinely offered chemotherapy, but due to expected adverse effects and frailty, elderly patients are often excluded from standard protocols. Colon cancer is a disease of the elderly and accordingly, there is a large subgroup of patients for which guidelines for adjuvant treatment remain less clear. In these two clinical settings, improved risk stratification has great potential impact on patient care, anticipating that high-risk patients will benefit from chemotherapy. However, microsatellite instability is the only molecular prognostic marker recommended for clinical use. EXPERIMENTAL DESIGN: In this perspective, we provide an updated view on the status and clinical potential of the many proposed prognostic gene expression-based tests for colon cancer stage II and III. RESULTS: The main limitation for clinical implementation is lack of prospective validation. For patients with stage II, highly promising tests have been identified and clinical trials are ongoing. For elderly patients with stage III, the value of such tests has received less focus, but promising early results have been shown. CONCLUSION: Although awaiting results from prospective trials, improved risk assessment for patients with stage II and III is likely to be achieved in the foreseeable future.

Sexual function in females after radiotherapy for rectal cancer.

BACKGROUND: Knowledge about female sexual problems after pre- or postoperative (chemo-)radiotherapy and radical resection of rectal cancer is limited. The aim of this study was to compare self-rated sexual functioning in women treated with or without radiotherapy (RT+ vs. RT-), at least two years after surgery for rectal cancer. METHODS AND MATERIALS: Female patients diagnosed from 1993 to 2003 were identified from a national database, the Norwegian Rectal Cancer Registry. Eligible patients were without recurrence or metastases at the time of the study. The Sexual function and Vaginal Changes Questionnaire (SVQ) was used to measure sexual functioning. RESULTS: Questionnaires were returned from 172 of 332 invited and eligible women (52%). The mean age was 65 years (range 42-79) and the time since surgery for rectal cancer was 4.5 years (range 2.6-12.4). Sexual interest was not significantly impaired in RT+ (n=62) compared to RT- (n=110) women. RT+ women reported more vaginal problems in terms of vaginal dryness (50% vs. 24%), dyspareunia (35% vs. 11%) and reduced vaginal dimension (35% vs. 6%) compared with RT- patients; however, they did not have significantly more worries about their sex life. CONCLUSION: An increased risk of dyspareunia and vaginal dryness was observed in women following surgery combined with (chemo-)radiotherapy compared with women treated with surgery alone. Further research is required to determine the effect of adjuvant therapy on female sexual function.