Comparison of Estimated Late Toxicities between IMPT and IMRT Based on Multivariable NTCP Models for High-Risk Prostate Cancers Treated with Pelvic Nodal Radiation.

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 >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.

Total marrow and lymphoid irradiation with helical tomotherapy: a practical implementation report.

PURPOSE: 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.

Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation.

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.

Primary amelanotic melanoma of the nasal cavity: a case report.

Primary mucosal malignant melanomas of the nose are rare, accounting for only 0.3 to 2% of all cases of malignant melanoma and about 4% of all head and neck melanomas. The amelanotic variant of mucosal malignant melanoma is even more rare, and the prognosis is poor. This variant usually arises in locations in which it is not noticeable, and therefore it is usually diagnosed at an advanced clinical stage when symptoms eventually manifest. We report a case of locally advanced amelanotic melanoma of the nasal cavity in a 55-year-old woman who presented with complaints of nasal obstruction and intermittent bleeding on the right side of the nose for 3 months and a gradually progressive diffuse swelling over the right periorbital and maxillary areas for 2 months with associated pain for 15 days. She was diagnosed with amelanotic melanoma on the basis of clinical, radiologic, and pathologic findings. In view of her advanced disease, she declined surgery and was treated with chemoradiotherapy, and she experienced a significant alleviation of her symptoms.

Filariasis, with chyluria and nephrotic range proteinuria.

28 yr female presented with (grade III) chyluria, with nephrotic range proteinuria and Ig M mesangial deposition in immunofluorescence, secondary to filariasis which was confirmed by serology and microfilaria in glomerulus,and successfully treated by Renal Pelvic instillation sclerotherapy with 0.2% povidine and medical treatment (Diethylcarbamazine). She was asymptomatic with follow up period of 19 months.

Adjuvant treatment of unresectable choroid plexus carcinoma with literature review.

Choroid plexus carcinomas are rare and arise from the choroid plexus, with invariably poor prognosis. We report an unusual case of an 8-year old male who presented with symptoms of increased intracranial pressure with radiological evidence of brain intraventricular lesion which was proved to be choroid plexus carcinoma on histopathology and immunohistochemistry. Treatment consisted of limited surgery followed by craniospinal irradiation and boost to the local tumor. Post treatment there was evidence of residual disease with no significant clinical improvement for which patient was managed conservatively with steroids along with chemotherapy with poor outcome. Hence aggressive surgical resection of the tumor is the most relevant prognostic predictor for survival, and is associated with poor prognosis if not completely excised irrespective of adjuvant treatment.

Esthesioneuroblastoma chemotherapy and radiotherapy for extensive disease: a case report.

Malignant tumors of the nasal cavity are rare. We report the case of a 48 years old man who consulted us with a 2-year history of progressive nasal obstruction, occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. On staging, the mass was classified as a Kadish stage C tumor with extensive involvement of the nasal cavities, nasopharynx, paranasal sinuses and orbit. Endoscopic excision of the mass was done. Traditionally the mainstay of treatment in such locally advanced patients is craniofacial resection followed by adjuvant radiotherapy. Our patient was treated with limited surgery and chemoradiation. Patient is free of recurrence at a follow-up of 5 years. This case report demonstrates the potential efficacy of planned combined modality therapy, including limited surgery and early chemoradiation in the control of locally advanced olfactory neuroblastoma.

Clinical benefits of two different dosing schedules of recombinant human erythropoietin in anemic patients with advanced head and neck cancer.

A total of 100 patients with stage III or IV head or neck cancer, a performance status of 0-1, and anemia with hemoglobin (Hb) < 10 g/dL at baseline who where to receive chemotherapy concomitantly or sequentially with radiotherapy were randomized to receive either epoetin beta 10,000 IU thrice weekly (TW) (n = 52) and oral iron starting 10-15 days before the start of treatment or epoetin beta 30,000 IU once weekly (OW) (n = 48) and oral iron before the start of treatment. The mean Hb in patients on the thrice weekly (11.96 g/dL) and once weekly (12.50 g/dL) dosing schedules increased significantly (p < 0.01) at the end of the treatment in comparison to respective baseline values of 9.38 g/dL and 9.41 g/dL; levels were 1.2-fold higher, which was significant (p < 0.01), for patients on the once weekly schedule. That said, there was significant improvement (p < 0.01) in mean linear analog scale assessment (LASA) scores for energy level (EL), ability to perform daily activities (AL), and overall quality of life (QOL) for patients on both dosing schedules but these improvements did not differ significantly between schedules (p > 0.05). The 2-year overall survival for patients on both dosing schedules did not differ significantly (p > 0.05). Epoetin beta therapy was found to be equally beneficial and well tolerated for patients on both thrice weekly and once weekly dosing schedules.

[Leishmaniasis--oral treatment with hexadecylphosphocholine]. / Leishmaniasis: Orale Therapie mit Hexadecylphosphocholin.

Hexadecylphosphocholine (HDPC, Miltefosine, Impavido) was synthesized at the Max-Planck-Institut für Biophysikalische Chemie in Göttingen, Germany and successfully used for the therapy of cancer metastases. At the Institute of General and Tropical Hygiene of Göttingen University the antiparasitic efficacy--earlier mentioned by Croft et al. (1987)--could be established for the first time in animals after oral administration. In India Impavido has been recently registered for the treatment of visceral leishmaniasis as the first oral medication in this indication. Clinical studies in India--actually a phase IV study is running--and Columbia (cutaneous leishmaniosis) demonstrated the excellent efficacy of this oral treatment also in patients with Antimon resistance. The cure rates are above 90% with low side effects (Impavido twice 50 mg capsules daily over 28 days).