M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis

BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Stressors in Breast Cancer Post-Treatment: a Qualitative Approach Factores estresantes del post-tratamiento del cáncer de mama: un enfoque cualitativo Estressores pós-tratamento do câncer de mama: um enfoque qualitativo

With the increasing effectiveness of breast cancer treatment, the scientific interest in investigating the quality of life of survivors has increased. However, research addressing the post-treatment period is still scarce. The aim of this study was to identify the stressors present in the lives of women in the one to five years post-diagnosis period. The sample was composed of 16 women assisted at a specialized mastectomy rehabilitation service. Data were collected through semi-structured interviews and analyzed using content analysis. The results indicate conflicts with self-image and alteration in the feeling of autonomy, fear in relation to the evolution of the condition, feelings of guilt about the disorder generated in the family, experience of disturbing social situations and a desire to return to their professional occupation. These results reveal the existence of stressors in this phase and the importance of support offered by psychosocial rehabilitation services for this population.<br>Con la creciente resolutividad del tratamiento del cáncer de mama, ha aumentado el interés científico por la investigación de la calidad de vida de las sobrevivientes. Sin embargo, todavía son escasas las investigaciones que abordan el período post-tratamiento. Este estudio tuvo por objetivo identificar los factores estresantes presentes en la vida de mujeres en el período de uno a cinco años post-diagnóstico. Fueron investigadas 16 mujeres atendidas en un servicio especializado en rehabilitación de mastectomizadas. Los datos fueron recolectados mediante entrevista semiestructurada y analizados por medio del análisis de contenido. Los resultados indicaron conflictos con la autoimagen, alteración en la sensación de autosuficiencia, miedo en relación a la evolución del cuadro, sentimiento de culpa por el trastorno generado en la familia, vivencia de situaciones sociales perturbadoras y, deseo de retornar a la ocupación profesional. Esos resultados refuerzan la comprobación de la existencia de factores estresantes en esta fase y la importancia del apoyo ofrecido por los servicios de rehabilitación psicosocial junto a esa población.<br>Com a crescente resolutividade do tratamento do câncer de mama, tem aumentado o interesse científico pela investigação da qualidade de vida das sobreviventes. No entanto, ainda são escassas as pesquisas que abordam o período pós-tratamento. Este estudo teve por objetivo identificar os estressores presentes na vida de mulheres, no período de um a cinco anos pós-diagnóstico. Foram investigadas 16 mulheres, atendidas em um serviço especializado em reabilitação de mastectomizadas. Os dados foram coletados mediante entrevista semiestruturada e analisados por meio da análise de conteúdo. Os resultados indicaram conflitos com a autoimagem e alteração na sensação de autossuficiência, medo em relação à evolução do quadro, sentimento de culpa pelo transtorno gerado na família, vivência de situações sociais perturbadoras e desejo de retornar à ocupação profissional. Esses resultados reforçam a existência de estressores nessa fase e a importância do apoio oferecido pelos serviços de reabilitação psicossocial, junto a essa população