Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.

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To standardize the technique; evaluate resources requirements and analyze our early experience of total marrow and lymphoid irradiation (TMLI) as part of the conditioning regimen before allogenic bone marrow transplantation using helical tomotherapy. Materials and Methods: Computed tomography (CT) scanning and treatment were performed in head first supine (HFS) and feet first supine (FFS) orientations with an overlap at mid-thigh. Patients along with the immobilization device were manually rotated by 180° to change the orientation after the delivery of HFS plan. The dose at the junction was contributed by a complementary dose gradient from each of the plans. Plan was to deliver 95% of 12 Gy to 98% of clinical target volume with dose heterogeneity <10% and pre-specified organs-at-risk dose constraints. Megavoltage-CT was used for position verification before each fraction. Patient specific quality assurance and in vivo film dosimetry to verify junction dose were performed in all patients. Results: Treatment was delivered in two daily fractions of 2 Gy each for 3 days with at least 8-hour gap between each fraction. The target coverage goals were met in all the patients. The average person-hours per patient were 16.5, 21.5, and 25.75 for radiation oncologist, radiation therapist, and medical physicist, respectively. Average in-room time per patient was 9.25 hours with an average beam-on time of 3.32 hours for all the 6 fractions. Conclusion: This report comprehensively describes technique and resource requirements for TMLI and would serve as a practical guide for departments keen to start this service. Despite being time and labor intensive, it can be implemented safely and robustly.

Purpose To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen. Materials and Methods Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance. Results Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP &gt;10%, 67% (8 patients) would be eligible for PBT. Conclusion Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.