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Comparison of Three Different Induction Regimens for Nasopharyngeal Cancer

BACKGROUND The standard treatment of local advanced nasopharyngeal cancer is chemoradiotherapy. There is a lack of data concerning induction therapy. In this study we retrospectively examined patients treated with induction therapy and chemoradiotherapy. MATERIALS AND METHODS Locally advanced nasopharyngeal cancer patients treated between 1996 and 2013 in our clinic were included in the study. Three different induction regimens were administered to our patients in different time periods. The regimen dosages were: CF regimen, cisplatin 50mg/m2 1-2 days, fluorouracil 500mg/m2 1-5 days; DC, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day; and DCF, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day, 5-Fu 750mg/m2 1-5 days. Most of the patients were stage III (36.4%) and stage IV (51.7%). RESULTS Median follow-up time was 50 months (2-201 months). Three-year progression-free survival (PFS) was 79.3%, and 5-year PFS 72.4% in all patients. Three-year overall survival (OS) was 87.4% and 5-year OS 76% in all patients. In terms of induction therapies, 3-year OS was 96.5% in the DCF group, 86.6% in the DC group and 76.3% in the CF group (p=0.03). CONCLUSIONS There was no significant differences in response rate and PFS between the three regimens. OS in the DCF group was significantly higher than in the other groups. However, this study was retrospective and limited toxicity data were available; the findings therefore need to be interpreted with care.

Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcoma

Leiomyosarcomas (LMS) are rare tumors with poor prognosis owing to the high rate of recurrent and metastatic disease. The combination of doxorubicin (Adriamycin) plus ifosfamide and mesna (AIM) results in moderate response rates of 10%-30%. The aim of this study was to assess the efficacy of the AIM regimen along with multimodality treatment including surgery and radiotherapy in patients with LMS. The clinicopathologic characteristics and outcomes of 51 patients with recurrent or metastatic LMS diagnosed between 2000 and 2014 who received the AIM regimen were analyzed retrospectively. Treatment consisted of ifosfamide 2500mg/m² on days 1-3 (with mesna 2500mg/m² days 1-3, 4-hour i.v. infusion), and doxorubicin 60mg/m² on day 1 (2-hour i.v. infusion), which was repeated every 21 days. The mean age of the patients at diagnosis was 48.9 ± 11.2 years. A total of 42 patients were females (82.4%). The primary tumor site was the uterus in 30 (58.8%) patients. The most common metastatic sites were lung and liver. The median follow-up was 27.9 months (min: 4.3 max: 164.8). The median progression-free survival was 6.7 months (95% CI: 4.1-9.2). The median overall survival (OS) was 24.6 months (95% CI: 16.2-33.0). The overall response rate was 12% (6/51 pts). Response rates were higher in patients with uterine LMS (17%) compared with those with nonuterine LMS (5%); however, the OS times were similar. Surgical intervention for local or distant recurrence was associated with improved median OS (41 vs 16.6 months, P < 0.001). Myelosuppression was the major toxicity of this combination. In our study, the AIM regimen was effective in patients with LMS. Resection of local or distant recurrence was found to improve survival in our study.

Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial Neoplasms

We read with interest the article by Choe et al. entitled ‘‘Improved Survival with Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial Neoplasms’’ published early online in Annals of Surgical Oncology. The authors reported a 34-month improvement in overall survival with addition of anti-vascular endothelial growth factor (VEGF) therapies to cytotoxic chemotherapy (CT) in patients with unresectable appendiceal neoplasms. However, as we noticed in Table 1 (and also stated by the authors in their discussion), 95% of patients who received a biologic agent were treated with doublet chemotherapy (fluoropyrimidine plus oxaliplatin/ irinotecan) while only 40% of patients in the ‘‘non-biological group’’ received doublet chemotherapy. Benefit of adding oxaliplatin or irinotecan to a fluoropyrimidine had previously been shown in phase III studies in colorectal cancer in terms of progression-free survival (PFS) or overall survival (OS). Therefore, differences in the chemotherapy backbone might also account for such an outstanding difference in PFS and OS between the treatment groups in the present study. The authors state that comparison of CT backbones was not the purpose of this study and that the same treatment principles of colorectal cancer would not be applicable to appendiceal cancer, however such discordance in the frequency of doublet CT use will probably confound the treatment effect of biological agents and should at least be included in the multivariate analysis to refine the benefit of biological agents. The multivariate analyses presented in Tables 2 and 3 are not useful in this sense, as they report neither the effect of the CT regimen (single agent versus doublet) nor, very interestingly, the effect of anti-VEGF therapy. In fact, it is very confusing to not be able to find a mention of the primary study parameter in the tables of a manuscript presenting multivariate analyses. That being the case, proposing an improvement in OS and PFS with bevacizumab without refining the confounding effect of CT backbone is probably misleading. Addition of the CT regimen type to the multivariate analysis might probably extenuate, if not eliminate, the magnitude of the benefit of anti-VEGF therapy and might provide a better message for readers until randomized trials with bevacizumab are conducted in this patient population.

Interpretation of survival data: which graphical analysis is appropriate?

We read with great interest the comprehensive review on the treatment of unresectable metastatic colorectal cancer by Chibaudel and colleagues [Chibaudel et al. 2015]. The authors analyzed current data on the initial treatment, maintenance therapy, second-line therapy and beyond, in a concise fashion. As mentioned in the manuscript, the choice of the biologic agent in the first-line treatment of RAS wild-type metastatic colorectal cancer is debatable because of the inconsistent results of the two large randomized trials. We have concerns on the interpretation of the combined information from CALGB/SWOG 80405 and AIO FIRE-3 studies in this manuscript. In our opinion, for the two studies in their Figure 2, the analytical approach, the inference, and the graphical presentation (Figure 2C) derived from this approach are imprecise. One key assumption in the Cox model is proportional hazards, which means that the survival curves for two strata must have hazard functions that are proportional over time [Cox, 1972]. When the proportional hazards assumption is violated, various approaches may help overcome the problem, by providing insight into the nature of the nonproportionality and how to modify the Cox model to best fit the data. However, the graphical analysis performed by the authors involves some degree of subjectivity in interpretation. In Graphs A and B, the boundaries of ‘superiority’, ‘uncertain’ and ‘no superiority’ are subjective, considering the effect size and the missing confidence intervals. The percentages on the combined analysis in Graph C is produced simply by finding the average of the values of the corresponding percentages in Graphs A and B. Such a descriptive approach ignores any methodological improvement which followed the introduction of the meta-analytical thinking by iconic statisticians such as Pearson and Fisher at the beginning of the 20th century [O’Rourke, 2007]. Therefore, the conclusion statement proposing the ‘probably unquestionable superiority of EGFR monoclonal antibodies over bevacizumab in 20% of all patients’ is below the standards of statistical inference. The extended exploration of graphics might be helpful tool in describing time segments with nonproportional hazards, but should not be the basis of simple mathematical calculations upon which a treatment decision is made.

Analysis of the Adjuvant Hormone Therapy Randomized Trial

period of AHTuse was 1.14 years. Such a short period of treatment was associated with a 33% reduction in the risk of ovarian cancer recurrence (hazard ratio, 0.67; 95% CI, 0.47 to 0.97). When compared with the magnitude of benefit from tamoxifen in breast cancer(treatment of5yearswasassociatedwitha39%reduction in the risk of recurrence), 10 this finding is striking and should be validated in larger cohorts before widespread use can be suggested.

Nasopharyngeal sarcoidosis: a rare involvement

Sarcoidosis is a chronic, multisystemic, non-caseating granulomatous disease of unknown etiology. Nasopharyngeal involvement is very rare in sarcoidosis. The objective of this report was to evaluate a rare involvement of sarcoidosis. This report includes a case of nasopharyngeal sarcoidosis. A 51-year-old female with nasopharyngeal sarcoidosis was treated as sarcoidosis, and she was better. Nasopharyngeal involvement is very rare in sarcoidosis but it must be kept in mind.