Deepak D. Deshpande

Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

PURPOSE To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). METHODS AND MATERIALS Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. RESULTS Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. CONCLUSION Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

NASOPHARYNGEAL CARCINOMA IN CHILDREN: COMPARISON OF CONVENTIONAL AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. PATIENTS AND METHODS A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. RESULTS After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. CONCLUSION The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

PURPOSE Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging. MATERIALS AND METHODS Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus. RESULTS Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R=0.92 and 0.94 (p<0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R=0.63 and 0.82 (p<0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively. CONCLUSIONS Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.

Perioperative Interstitial Brachytherapy for Soft Tissue Sarcomas: Prognostic Factors and Long-Term Results of 155 Patients

BackgroundThe goal of this study was to evaluate the efficacy of temporary interstitial brachytherapy (BRT) for patients undergoing combined modality management of soft tissue sarcomas (STS).MethodsFrom January 1990 to December 2003, 155 adults 18–88 years of age (median = 42 years) with STS who had received BRT as part of locoregional treatment were included in this review. Sixty-four percent were males. Sixty-nine percent had primary lesions. Sixty percent had lesions involving the lower extremities. Spindle cell sarcoma (28%) and synovial sarcoma (16%) were the most common histologic types and 51% had grade III lesions. Treatment included wide local excision of primary tumor with BRT with or without external beam radiotherapy (EBRT).ResultsAfter a median followup of 45 months, the local control (LC), disease-free survival (DFS), and overall survival (OS) for the entire cohort was 71%, 57%, and 73%, respectively. DFS was superior for superficial tumors compared with that for deep tumors (96% vs. 54%, P =.02). Patients with a tumor less than 5 cm had superior OS (88% vs. 63%, P =.05). Cumulative radiotherapy dose greater than 60 Gy had a significant positive impact on LC (P = .003), DFS (P =.003), and OS (P =.048). Subcutaneous fibrosis (21%) was the major complication.ConclusionsTemporary perioperative iridium-192 interstitial BRT with or without EBRT after function-preserving surgery results in satisfactory outcome in patients with STS. Both low dose rate and high dose rate BRT are equivalent in terms of disease control and complications when used alone or in combination with EBRT. BRT results in fewer complications compared with the combination of BRT and EBRT.

Inter-application variation of dose and spatial location of D 2 cm 3 volumes of OARs during MR image based cervix brachytherapy

PURPOSE Evaluation of Inter-application variation of doses and spatial location of D(2cm(3)) volumes of OARs during MR-image based cervix brachytherapy. MATERIALS AND METHODS Twenty-seven patients treated with EMBRACE protocol were analyzed. Every patient had two applications, one week apart. For each application patient had undergone MR-imaging (MR-1 and MR-2), volume delineation, reconstruction, treatment planning (plan-1 and plan-2) and dose evaluation. Both the image series were then co-registered with applicator as the reference coordinate system (Eclipse planning system v8.6.14). Inter-application dose, volume and spatial location of D(2cm(3)) variation were evaluated. RESULTS The largest inter-application systematic and random dose variations were observed for sigmoid as compared to rectum and bladder. The mean (±SD) of the relative D(2cm(3)) variations were 0.6(±15.1)%, 0.9(±13.1)% and 11.9(±37.5)% for rectum, bladder and sigmoid respectively. The overlap of D(2cm(3)) volumes was more than 50% in 16(59%), 8(30%) and 3(11%) patients for rectum, bladder and sigmoid, respectively. CONCLUSION The 2cm(3) volumes between the applications/fractions are quite stable in topography for bladder and rectum, and hence the current practice of cumulative addition of D(2cm(3)) dose is expected to be valid for bladder and rectum. For sigmoid, significant topographical changes were seen, which need further validation in a larger patient population and in multi-centric settings.

Dosimetry of intracavitary applications in carcinoma of the cervix: rectal dose analysis

The International Commission on Radiation Units and Measurements (ICRU), in its Report-38, has given certain recommendations regarding the specifications of bladder and rectal reference points in the intracavitary treatment of carcinoma of the cervix. Conforming to this report, 182 intracavitary applications performed in stage I and II cervix cases were analyzed. In 113 applications, the maximum rectal dose was found to be in a point on the anteroposterior line drawn through the centre of colpostat sources. However, for our type of applications, the point on the anteroposterior line drawn through the lower end of the uterine tube seldom gets maximum dose. In addition, it was observed that there are other dose points than the ICRU reference point receiving doses close to maximum dose. It was concluded that doses to multiple rectal reference points should be recorded, in addition to the ICRU-defined rectal reference point.

Reporting and validation of gynaecological Groupe Euopeen de Curietherapie European Society for Therapeutic Radiology and Oncology (ESTRO) brachytherapy recommendations for MR image-based dose volume parameters and clinical outcome with high dose-rate brachytherapy in cervical cancers: a single-institution initial experience.

Objective: The objectives are to report the dosimetric analysis, preliminary clinical outcome, and comparison with published data of 3-dimensional magnetic resonance-based high dose rate brachytherapy (BT) in cervical cancer. Materials and Methods: The data set of 24 patients with cervical cancer treated with high dose-rate brachytherapy applications was analyzed. All patients received radiation with or without chemotherapy (10 patients received concomitant chemoradiation). Point A, International Commission on Radiation Units and Measurement (ICRU) point doses, and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology dose volume parameters, namely, high-risk clinical target volume (HR-CTV), D90 and D100 doses, and dose to D0.1cc and D2cc, for rectum, bladder, and sigmoid, were calculated and correlated. Results: Mean ± SD HR-CTV was 45.2 ± 15.8 cc. The mean ± SD point A dose was 73.4 ± 4.5 Gy (median, 74.3 Gy) total biologically equivalent dose in 2 Gy per fraction (EQD2), whereas mean ± SD D90 doses were 70.9 ± 10.6 GyEQD2 (median, 68). The mean ± SD ICRU rectal and bladder points were 63.5 ± 8.1 and 80.4 ± 34.4 GyEQD2, respectively. The D0.1cc and D2cc for rectum were 66.0 ± 9.9 GyEQD2 (median, 64.5) and 57.8 ± 7.7 GyEQD2 (median, 58.8), for bladder 139.1 ± 54.7 GyEQD2 (median, 131.9) and 93.4 ± 24.6 GyEQD2 (median, 91), and sigmoid were 109.4 ± 45.2 GyEQD2 (median, 91) and 74.6 ± 19.6 GyEQD2 (median, 69.6). With a median follow-up of 24 months, 3 patients had local nodal failure, 1 had right external iliac nodal failure, and 1 had left supraclavicular nodal failure. Conclusions: The 3-D magnetic resonance image-based high dose-rate brachytherapy approach in cervical cancers is feasible. In our experience, the HR-CTV volumes are large, and D0.1cc and D2cc doses to bladder and sigmoid are higher than published literature so far.

Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.

PURPOSE Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. MATERIALS AND METHODS Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. RESULTS The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. CONCLUSIONS Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern.

Dosimetric evaluation of a new OneDose MOSFET for Ir-192 energy

The purpose of this study was to investigate dosimetry (reproducibility, energy correction, relative response with distance from source, linearity with threshold dose, rate of fading, temperature and angular dependence) of a newly designed OneDosetrade mark MOSFET patient dosimetry system for use in HDR brachytherapy with Ir-192 energy. All measurements were performed with a MicroSelectron HDR unit and OneDose MOSFET detectors. All dosimeters were normalized to 3 min post-irradiation to minimize fading effects. All dosimeters gave reproducible readings with mean deviation of 1.8% (SD 0.4) and 2.4% (SD 0.6) for 0 degrees and 180 degrees incidences, respectively. The mean energy correction factor was found to be 1.1 (range 1.06-1.12). Overall, there was 60% and 40% mean response of the MOSFET at 2 and 3 cm, respectively, from the source. MOSFET results showed good agreement with TLD and parallel plate ion chamber. Linear dose response with threshold voltage shift was observed with applied doses of 0.3 Gy-5 Gy with Ir-192 energy. Linearity (R2 = 1) was observed in the MOSFET signal with the applied dose range of 0.3 Gy-5 Gy with Ir-192 energy. Fading effects were less than 1% after 10 min and the MOSFET detectors stayed stable (within 5%) over a period of 1 month. The MOSFET response was found to be decreased by approximately 1.5% at 37 degrees C compared to 20 degrees C. The isotropic response of the MOSFET was found to be within +/-6%. A maximum deviation of 5.5% was obtained between 0 degrees and 180 degrees for both the axes and this should be considered in clinical applications. The small size, cable-less, instant readout, permanent storage of dose and ease of use make the MOSFET a novel dosimeter and beneficial to patients for skin dose measurements with HDRBT using an Ir-192 source compared to the labour demanding and time-consuming TLDs.

Skin dose measurements using MOSFET and TLD for head and neck patients treated with tomotherapy.

The purpose of this work was to estimate skin dose for the patients treated with tomotherapy using metal oxide semiconductor field-effect transistors (MOSFETs) and thermoluminescent dosimeters (TLDs). In vivo measurements were performed for two head and neck patients treated with tomotherapy and compared to TLD measurements. The measurements were subsequently carried out for five days to estimate the inter-fraction deviations in MOSFET measurements. The variation between skin dose measured with MOSFET and TLD for first patient was 2.2%. Similarly, the variation of 2.3% was observed between skin dose measured with MOSFET and TLD for second patient. The tomotherapy treatment planning system overestimated the skin dose as much as by 10-12% when compared to both MOSFET and TLD. However, the MOSFET measured patient skin doses also had good reproducibility, with inter-fraction deviations ranging from 1% to 1.4%. MOSFETs may be used as a viable dosimeter for measuring skin dose in areas where the treatment planning system may not be accurate.