Marianne Grønlie Guren

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

BACKGROUND As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

LATE SIDE EFFECTS AND QUALITY OF LIFE AFTER RADIOTHERAPY FOR RECTAL CANCER

PURPOSE There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535). METHODS AND MATERIALS All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). RESULTS Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non-radiation-treated (RT-) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT- patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT- patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001). CONCLUSIONS Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

Quality of life during radiotherapy for rectal cancer

The aim of this study was to assess symptoms and health-related quality of life (HRQL) during (neo)adjuvant radiotherapy for rectal cancer. Patients receiving pelvic radiotherapy 50 Gy for rectal cancer, were studied prospectively (n=42). The European Organization for Research and Treatment of Cancer (EORTC) questionnaires quality of life-core 30 QLQ-C30 and QLQ-CR38 and a 5-day symptom diary were completed at the start and end of radiotherapy and 4-6 weeks later. At the end of radiotherapy, mean scores of diarrhoea, fatigue and appetite loss had significantly increased (P<0.01) compared with pretreatment scores, but this was not observed for scores for nausea or pain. At the end of radiotherapy, diarrhoea, fatigue, appetite loss, physical function, social function and global quality of life (QL) were significantly worse than the population-based norms. 64% of the patients reported an increase in fatigue and 52% an increase in diarrhoea during radiotherapy. HRQL scores had returned to pre-treatment levels 4-6 weeks after radiotherapy. Thus, diarrhoea, fatigue and appetite loss increased transiently during pelvic radiotherapy.

Sexual Function in Males After Radiotherapy for Rectal Cancer

PURPOSE Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer. METHODS AND MATERIALS Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured. RESULTS Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT- patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate-severe erectile dysfunction in RT+ patients was 7.3 compared with RT- patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01). CONCLUSION RT for rectal cancer is associated with significant long-term effects on sexual function in males.

Sexual function in females after radiotherapy for rectal cancer

Abstract 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.

Impaired health-related quality of life after chemoradiotherapy for anal cancer: Late effects in a national cohort of 128 survivors

Abstract Background. Chemoradiotherapy is an effective treatment for anal cancer, yet from follow-up many survivors seem to suffer from late effects. Data of long-term health-related quality of life (HRQOL) in anal cancer survivors are limited, and there is a growing interest in cancer survivorship. Material and methods. A national cohort of all anal cancer survivors treated with curative chemoradiotherapy in 2000–2007 was invited to a cross-sectional study. Of 199 eligible survivors, 128 (64%) returned the questionnaires, the median time since diagnosis was 66 months. The median age was 61 years and 79% were women. HRQOL was evaluated with EORTC questionnaires QLQ-C30 and QLQ-CR29, and neurotoxicity with the Scale of Chemotherapy-Induced Neurotoxicity. An age- and sex-matched reference group of volunteers (n = 269) not treated for pelvic cancer answered the same questionnaires. Results from QLQ-C30 of the reference group were compared to Norwegian and Dutch normative data. Results. The mean scores of anal cancer survivors were poorer compared to volunteers and normative data. Anal cancer survivors reported significant impairment of function, especially social and role function, compared to the volunteers (difference ≥ 20 points, p < 0.001). Survivors had markedly increased scores for fatigue, dyspnoea, insomnia and diarrhoea (difference ≥ 15 points, p < 0.001). The global quality of life was significantly reduced (difference 15 points, p < 0.001). Anal cancer survivors had increased stool frequency, more buttock pain, flatulence, faecal incontinence, impotence (males), dyspareunia and reduced sexual interest (females) (difference ≥ 15 points, p < 0.001). There was increased frequency of tinnitus in survivors treated with cisplatin-based chemotherapy (p = 0.004). Conclusions. Survivors after chemoradiotherapy for anal cancer have significant long-term impairment of HRQOL. Reduced social, role and sexual function, and increased diarrhoea, incontinence for gas and stools, and buttock pain were commonly reported. Increased awareness of this may lead to better management of late effects and better care for cancer survivors.

Is England closing the international gap in cancer survival

Background:We provide an up-to-date international comparison of cancer survival, assessing whether England is ‘closing the gap’ compared with other high-income countries.Methods:Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995–2012. Trends during 1995–2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends.Results:Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005–2009. For some cancers, survival improved more in England than in other countries between 1995–1999 and 2005–2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010–2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995–1999 and 2005–2009.Conclusions:Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap.

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

PURPOSE It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. METHODS AND MATERIALS All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. RESULTS Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. CONCLUSIONS Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

Radiation therapy induced changes in male sex hormone levels in rectal cancer patients

BACKGROUND AND PURPOSE To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. MATERIALS AND METHODS Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. RESULTS Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). CONCLUSION Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years.

Palliative pelvic radiotherapy of symptomatic incurable rectal cancer - a systematic review

Abstract Background. Locally advanced and recurrent rectal cancers frequently cause pelvic morbidity including pain, bleeding and mass effect. Palliative pelvic radiotherapy is used to relieve these symptoms and delay local progression. There is no established optimal radiotherapy regimen and clinical practices vary. Our aim was to review the efficacy and toxicity of palliative pelvic radiotherapy of symptomatic rectal cancer and to evaluate different fractionation schedules, based on published literature. Material and methods. Systematic literature searches of Medline, Embase and Cochrane databases were performed through 2011. Studies reporting symptomatic response or quality of life (QOL) after palliative radiotherapy for rectal or rectosigmoid cancer were eligible. Results. Twenty-seven studies were included, of which 23 were retrospective reviews. There were no patient-reported outcomes or QOL assessments. There were large variations in applied radiotherapy regimens. Pooled overall symptom response rate was 75% and positive responses were reported for pain (78%), bleeding and discharge (81%), mass effect (71%) and other pelvic symptoms (72%). Toxicity results were not evaluable. Conclusion. Palliative pelvic radiotherapy for symptomatic rectal cancer appears to provide relief of a variety of pelvic symptoms, although there is no documented optimal radiotherapy regimen in this context. There is inadequate evidence regarding onset, duration and degree of symptom palliation, QOL and associated toxicity with this treatment and prospective studies are therefore needed.