AIM:Women with a history of human papillomavirus (HPV)-related cervical, vaginal or vulvar high-grade squamous intra-epithelial lesions (HSILs) or cancer are at increased risk of developing anal squamous intra-epithelial lesions (SILs) or a squamous cell carcinoma of the anus (SCCA). Screening for intra-anal SILs with high-resolution anoscopy (HRA) in high-risk populations is a subject of debate. In this study we aimed to answer the following question: what is the prevalence of intra-anal (H)SIL in women with HPV-related vulvar and/or perianal disease using HRA for screening?METHOD:A retrospective study was performed to evaluate the prevalence of intra-anal (H)SIL in women with a history of vulvar and/or perianal HSIL or (superficially invasive) squamous cell carcinoma (SCC). This study was performed between 2015 and 2018 following implementation of a protocol for intra-anal screening using HRA.RESULTS:Twenty-seven patients, 10 with a history of (superficially invasive) SCC (four vulvar, five perianal, one multizonal) and 17 with HSIL as the worst diagnosis (two perianal, 15 multizonal) were screened for intra-anal lesions using HRA. No anal cancer was found at screening, 6 (22%) patients were diagnosed with intra-anal HSIL and 12 (44%) patients with intra-anal low-grade SIL.CONCLUSIONS:We found a high prevalence of intra-anal HSIL in women previously diagnosed with vulvar and perianal HSIL. Given the clear link between HSIL and SCCA, screening for intra-anal lesions in women with HPV-related genital pathology seems warranted. Future studies should focus on the effect of HSIL treatment on the prevention of anal cancer.

Background: Women with a human papillomavirus related history of cervical, vaginal or vulvar high-grade dysplasia or cancer are at increased risk to develop anal dysplasia or anal cancer. Screening for anal cancer precursors (squamous intraepithelial lesions (SIL)) with high resolution anoscopy (HRA) in high-risk populations is subject of debate. In this study we evaluated standardized intra-anal SIL screening using HRA in high-risk female patients. Methods: A retrospective observational study was performed to evaluate the prevalence of intra-anal SIL in women with a history of vulvar high-grade SIL (HSIL) and perianal HSIL diagnosed at the Netherlands Cancer Institute, who were referred for intra-anal SIL screening using HRA in the MC Slotervaart between 2015 and 2017. Results: 22 female patients were screened for anal SIL using HRA. 19 females had a history of biopsy proven vulvar HSIL and 19 females had a history of biopsy proven perianal HSIL. Eleven (50%) patients had a history of multizonal HSIL at three or more perianogenital locations. No anal cancer was found at screening, 7 (32%) patients were diagnosed with anal HSIL and 7 (32%) patients with low-grade anal SIL. Conclusions: We found a high prevalence of anal HSIL in women with HPV related lower genital tract dysplasia. Intra-anal SIL screening using HRA in this high risk population seems to be justified. However, HRA is an invasive screening method. Studying other, less invasive screening methods remains important.

Conclusions: All the treatment plans could meet the clinical therapy needs.The dose measurements also showed good agreement with computed doses.RapidArc technique can treat patients with advanced NPC effectively, with good target coverage and sparing of critical structures.RA has a slightly dosimetric superiority than RA-FFF.

Metastatic renal cell cancer is one of the immuno-sensitive tumors. Apart from the immuno-modulating agents IFNalpha and IL-2, thalidomide has been reported to be effective in this type of cancer. However, bone metastases and bulky metastases, show limited response to immunotherapy, are often site of recurrent disease and are therefore often treated later with radiotherapy. In this phase II study, we evaluated toxicity and efficacy of the combination of continuous low dose (1 mIU/m2) s.c. IL-2 and thalidomide (200 mg once daily) in 22 patients with progressive metastatic renal cell cancer. In addition, 13 soft tissue lesions and two bone metastases in 13 patients were concurrently treated with fractionated radiotherapy. T cell number and activation in blood was measured by immunoflowcytometry. Nearly all patients developed grade 1-2 toxicity consisting of fatigue, sensory neuropathy, constipation and dizziness. Five patients had a grade 3-4 toxic event: four patients with deep venous thrombosis requiring anticoagulant therapy, and one patient who developed radiation myelopathy. On systemic response evaluation ten patients showed ongoing SD with a mean progression free survival of 9 months. One patient showed a PR (at an irradiated site). Regarding local response to irradiation, seven lesions showed a PR for a mean time period of 8.7 months, whereas seven were stable for 6 months. The radiation response of one lesion was not evaluable. Immunoflowcytometry showed an increase in number and activation of lymphocytes (mainly Natural Killer--NK-cells), which was absent or even decreased in irradiated patients. The combination of sc. low dose IL-2, thalidomide and radiotherapy is feasible, but relatively toxic and does not lead to higher responses at non-irradiated sites. The combination of immunotherapy and concurrent radiotherapy is effective at 60% of the relatively large evaluable sites. Progressive myelopathy developed in one patient, possibly due to radiotherapy in combination with thalidomide.