Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer

Background: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue. Methods: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread. Results: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease. Conclusions: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease

Association between tumor response and postoperative morbidity after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma?

Aim: The recommended treatment for locally advanced gastroesophageal adenocarcinoma has changed to a multimodal approach including neoadjuvant chemotherapy. The aim of this study was to assess potential associations between response to neoadjuvant therapy and post-operative morbidity in patients with gastroesophageal adenocarcinoma.Methods: Sixty-one patients undergoing surgical resection of gastroesophageal adenocarcinoma following neoadjuvant chemotherapy were analyzed. Patients were dichotomized into histopathological responders (Becker grade Ia-II, n = 37) and nonresponders (Becker grade III, n = 24). Perioperative complications were assessed according to the Clavien-Dindo classification. An association between response to neoadjuvant chemotherapy and surgical complications was evaluated with the chi-square or Fisher test where appropriate.Results: Twenty over thirty-seven responders (54.1%) and 17/24 non-responders (70.8%) had perioperative complications of any grade (P = 0.19). The most frequent complications were anastomotic leakage, which had a higher incidence among non-responders (4/24; 16.7%) than responders (1/37; 2.7%; Fisher's test: P = 0.07); and pulmonary complications, which showed no difference in incidence between non-responders (11/24; 45.8%) and responders (13/37; 35.1%; P = 0.57).Conclusion: In patients undergoing resection of gastroesophageal adenocarcinoma after neoadjuvant chemotherapy, there was no association between response and incidence of perioperative complications. However, there was a borderline significant higher incidence of anastomotic leakage among non-responders

Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia

The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology