Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Completion surgery after chemoradiotherapy for cervical cancer - is there a role? UK Cancer Centre experience of hysterectomy post chemo-radiotherapy treatment for cervical cancer.

The standard treatment for locally advanced cervical cancer is chemo-radiotherapy. The presence of the residual disease after treatment is directly related to the relapse risk and to poor survival. There is a lack of consensus on the role of a subsequent surgery due to morbidity concerns. Oncological and peri-operative outcomes of completion surgery for cervical cancer were reviewed by retrospective descriptive analysis of the eligible cases between March 2012 and March 2016. Fifteen women were identified. Ten (66.7%) had a residual tumour on their post-treatment MRI. Surgical histology indicated a residual cancer in 26.7%. There were three distant recurrences. Bowel and urinary complications were most commonly reported. Offering surgery to women with a residual cervical tumour found on MRI after chemo-radiation is beneficial, despite clear risks from the dual-modality treatment. A less radical surgery is preferable. An MRI has a reasonable negative predictive value, but this study has highlighted the need to further examine the role of MRI in predicting the residual disease and recurrence. Impact statement What is already known on this subject? The standard treatment for locally advanced cervical cancer is chemo-radiotherapy. The presence of residual disease after treatment is directly related to the relapse risk and poor survival. There is a lack of consensus on the role of a subsequent surgery due to morbidity concerns. The current evidence in the UK is limited, but across the world it appears that surgery can be beneficial for patients with incomplete chemo-radiotherapy, for certain histological subtypes of cervical cancer or for bulky residual disease. What do the results of this study add? The mode of surgery is more debateable, and this study concludes that both the laparoscopic and open surgeries are acceptable, but that radical surgery should be avoided as this contributes to a significant post-operative morbidity. This study explores the role of MRI imaging in predicting the residual disease and cervical cancer recurrence, concluding that a negative MRI post-chemoradiotherapy has a good negative predictive value for squamous cell cervical cancer, but otherwise can be unreliable. What are the implications of these findings for clinical practice and/or further research? An additional explored role of the MRI in predicting a recurrence in a larger cohort will be required, and it is likely that an additional assessment with PET-CT scanning will improve specificity.

Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer.

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with 528,000 estimated new cases globally in 2012. A large majority (around 85%) of the disease burden occurs in low- and middle-income countries (LMICs), where it accounts for almost 12% of all female cancers. Treatment of stage IB2 cervical cancers, which sit between early and advanced disease, is controversial. Some centres prefer to treat these cancers by radical hysterectomy, with chemoradiotherapy reserved for those at high risk of recurrence. In the UK, we treat stage IB2 cervical cancers mainly with chemoradiotherapy, based on the rationale that a high percentage will have risk factors necessitating chemoradiotherapy postsurgery. There has been no systematic review to determine the best possible evidence in managing these cancers. OBJECTIVES: To determine if primary surgery for stage IB2 cervical cancer (type II or type III radical hysterectomy with lymphadenectomy) improves survival compared to primary chemoradiotherapy.To determine if primary surgery combined with postoperative adjuvant chemoradiotherapy, for stage IB2 cervical cancer increases patient morbidity in the management of stage IB2 cervical cancer compared to primary chemoradiotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3), MEDLINE via Ovid (1946 to April week 2, 2018) and Embase via Ovid (1980 to 2018 week 16). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies up to April 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing surgery to chemoradiotherapy in stage IB2 cervical cancers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data, assessed risk of bias and analysed data using standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 4968 records from the literature searches, but we did not identify any RCTs that compared primary surgery with chemoradiotherapy in stage IB2 cervical cancer.We found one NRS comparing surgery to chemoradiotherapy in IB2 and IIA2 cervical cancers which met the inclusion criteria. However, we were unable to obtain data for stage IB2 cancers only and considered the findings very uncertain due to a high risk of selection bias. AUTHORS' CONCLUSIONS: There is an absence of high-certainty evidence on the relative benefits and harms of primary radical hysterectomy versus primary chemoradiotherapy for stage IB2 cervical cancer. More research is needed on the different treatment options in stage IB2 cervical cancer, particularly with respect to survival, adverse effects, and quality of life to facilitate informed decision-making and individualised care.

Self management, joint protection and exercises in hand osteoarthritis: a randomised controlled trial with cost effectiveness analyses.

BACKGROUND: There is limited evidence for the clinical and cost effectiveness of occupational therapy (OT) approaches in the management of hand osteoarthritis (OA). Joint protection and hand exercises have been proposed by European guidelines, however the clinical and cost effectiveness of each intervention is unknown.This multicentre two-by-two factorial randomised controlled trial aims to address the following questions:• Is joint protection delivered by an OT more effective in reducing hand pain and disability than no joint protection in people with hand OA in primary care?• Are hand exercises delivered by an OT more effective in reducing hand pain and disability than no hand exercises in people with hand OA in primary care?• Which of the four management approaches explored within the study (leaflet and advice, joint protection, hand exercise, or joint protection and hand exercise combined) provides the most cost-effective use of health care resources METHODS/DESIGN: Participants aged 50 years and over registered at three general practices in North Staffordshire and Cheshire will be mailed a health survey questionnaire (estimated mailing sample n = 9,500). Those fulfilling the eligibility criteria on the health survey questionnaire will be invited to attend a clinical assessment to assess for the presence of hand or thumb base OA using the ACR criteria. Eligible participants will be randomised to one of four groups: leaflet and advice; joint protection (looking after your joints); hand exercises; or joint protection and hand exercises combined (estimated n = 252). The primary outcome measure will be the OARSI/OMERACT responder criteria combining hand pain and disability (measured using the AUSCAN) and global improvement, 6 months post-randomisation. Secondary outcomes will also be collected for example pain, functional limitation and quality of life. Outcomes will be collected at baseline and 3, 6 and 12 months post-randomisation. The main analysis will be on an intention to treat basis and will assess the clinical and cost effectiveness of joint protection and hand exercises for managing hand OA. DISCUSSION: The findings will improve the cost-effective evidence based management of hand OA. TRIAL REGISTRATION: identifier: ISRCTN33870549.