Approach to Radical Hysterectomy for Cervical Cancer in Pregnancy: Surgical Pathway and Ethical Considerations.

INTRODUCTION: Cervical cancer is currently the fourth most common cancer in women and in the poorest countries this neoplasia still represents a widespread and potentially lethal disease. We present a rare case of cervical cancer in pregnancy, analyzing the historical changes behind the procedure of radical hysterectomy for cervical cancer and discussing variations in surgical techniques and anatomical definitions that have since been proposed. RESULTS: We present the case of a 33-year-old patient who attended with vaginal bleeding in the second trimester of pregnancy. Examination revealed an abnormal looking cervix, with investigations concluding stage IIb squamous cell carcinoma. Following extensive discussion regarding management options, the patient went on to have a peripartum foetocidal type III nerve sparing radical Wertheim hysterectomy at 18 weeks gestation with conservation and transposition of the ovaries above the level of the pelvic brim. The patient recovered well without significant morbidity and received further input from fertility and psychological medical teams in addition to adjuvant treatment within the department of clinical oncology. DISCUSSION: This case represents several elements of great interest and learning. Notably, we highlight this both due to the surgical challenges that a gravid uterus presents in the execution of a radical hysterectomy; and regarding the compassionate care demonstrated by the team - not only in supporting the patient and her partner in a period of profound turmoil in terms of the management of their cancer diagnosis and unborn child, but also regarding the uncertainty in consideration of the oncological and fertility related outcomes. CONCLUSION: This manuscript adds to the growing literature on the appropriate use of radical surgery for cervical cancer, more specifically during pregnancy and in consideration of such ethical dilemma, where management guidelines do not exist to aid clinicians further in their provision of treatment.

Diet and nutrition in patients who have received pelvic radiotherapy: A mixed-methods study to explore dietary habits, nutritional awareness, and experiences of nutritional care.

OBJECTIVES: Individuals who have survived cancer may benefit from dietary modifications to improve quality of life and future health outcomes. The aim of this study was to explore dietary habits and experiences of nutritional support in patients with a cancer diagnosis who have received radiotherapy to the pelvic area. METHODS: A mixed-methods approach was used. Individuals diagnosed with a pelvic cancer (anal, bladder, rectal, and cancers of the reproductive organs), either undergoing or having completed pelvic radiotherapy 6 to 24 mo previously, were invited to participate in a postal survey. A purposive subsample was also invited to take part in telephone interviews. Thematic analysis of interview data was undertaken and integrated with data from quantitative analysis. RESULTS: The survey was completed by 254 (38%) respondents. Two-thirds of respondents (170) reported dietary changes since diagnosis; most notable changes were reduction of sugary foods (48%) and alcohol (41%). Receipt of support from the health care team was significantly associated with dietary change (odds ratio, 3.26; 95% confidence interval, 1.58-6.75); however, only 43% (108) had received dietary support from the health care team. Of the respondents, 68% (171) said they would like to receive additional dietary support. The effect of the condition on diet was highlighted in the theme "Impact of diagnosis and treatments on dietary choices." Self-management of disease was influenced by personal resources, social resources, comorbidities and disabilities, influence of work, regaining normality, and barriers to dietary changes. CONCLUSION: Lack of routine provision of nutritional care to patients after a cancer diagnosis and patient interest in this area highlighted unmet needs in managing diet-related problems and leading a healthy future lifestyle.

Buparlisib with thoracic radiotherapy and its effect on tumour hypoxia: A phase I study in patients with advanced non-small cell lung carcinoma.

BACKGROUND: Pre-clinically, phosphoinositide 3-kinase (PI3K) inhibition radiosensitises tumours by increasing intrinsic radiosensitivity and by reducing tumour hypoxia. We assessed whether buparlisib, a class 1 PI3K inhibitor, can be safely combined with radiotherapy in patients with non-small cell lung carcinoma (NSCLC) and investigated its effect on tumour hypoxia. METHODS: This was a 3 + 3 dose escalation and dose expansion phase I trial in patients with advanced NSCLC. Buparlisib dose levels were 50 mg, 80 mg and 100 mg once daily orally for 2 weeks, with palliative thoracic radiotherapy (20 Gy in 5 fractions) delivered during week 2. Tumour hypoxic volume (HV) was measured using 18F-fluoromisonidazole positron-emission tomography-computed tomography at baseline and following 1 week of buparlisib. RESULTS: Twenty-one patients were recruited with 9 patients evaluable for maximum tolerated dose (MTD) analysis. No dose-limiting toxicity was reported; therefore, 100 mg was declared the MTD, and 10 patients received this dose in the expansion phase. Ninety-four percent of treatment-related adverse events were ≤grade 2 with fatigue (67%), nausea (24%) and decreased appetite (19%) most common per patient. One serious adverse event (grade 3 hypoalbuminaemia) was possibly related to buparlisib. No unexpected radiotherapy toxicity was reported. Ten (67%) of 15 patients evaluable for imaging analysis were responders with 20% median reduction in HV at the MTD. CONCLUSION: This is the first clinical trial to combine a PI3K inhibitor with radiotherapy in NSCLC and investigate the effects of PI3K inhibition on tumour hypoxia. This combination was well tolerated and PI3K inhibition reduced hypoxia, warranting investigation into whether this novel class of radiosensitisers can improve radiotherapy outcomes.

Cervical cancer.

INTRODUCTION: Worldwide, cervical cancer is the second most common cancer in women. The peak prevalence of infection is 20-30% in women aged 20-30 years, but in 80% of cases the infection resolves within 12-18 months. In the UK, incidence fell after introduction of the cervical-screening programme, to the current level of approximately 3200 cases and 1000 deaths a year. Survival ranges from almost 100% 5-year disease-free survival for treated stage Ia disease to 5-15% in stage IV disease. Survival is also influenced by tumour bulk, age, and comorbid conditions. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to manage early-stage cervical cancer? What are the effects of interventions to manage bulky early-stage cervical cancer? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: HPV vaccine for preventing cervical cancer and conisation of the cervix for microinvasive carcinoma (stage Ia1), neoadjuvant chemotherapy, radiotherapy, chemoradiotherapy, or different types of surgery for treating early stage and bulky early stage cervical cancer.