S.K. Shrivastava

INFLUENCE OF DOSE-RATE AND DOSE PER FRACTION ON CLINICAL OUTCOME OF BREAST CANCER TREATED BY EXTERNAL BEAM IRRADIATION PLUS IRIDIUM-192 IMPLANTS: ANALYSIS OF 289 CASES

PURPOSE To study the influence of Iridium 192 implant dose-rate and dose per fraction of external irradiation on clinical outcome, the results in 289 patients with early breast cancer were analyzed retrospectively. METHODS AND MATERIALS From 1980 to 1990, 118 T1 and 171 T2 lesions of breast were treated definitively by radiotherapy, following conservative surgery. External irradiation dose of 45 Gy was delivered either with 2.5 Gy or 1.8 Gy per fraction to the entire target volume, plus boost to the primary tumor. Boost dose of 15 to 30 Gy was given to the primary tumor either with iridium-192 implants or electrons. The implant dose-rate varied between 20 cGy/hr to 160 cGy/hr. RESULTS The minimum follow-up was of 12 months and maximum of 11 years (median: 56 months). Out of 273 tumors boosted with implants, the 270 patients were divided into five groups according to dose-rate as, groups 1 (20-29 cGy/hr, n = 17), group 2 (30-49 cGy/hr, n = 144), group 3 (50-69 cGy/hr, n = 69), group 4 (70-99 cGy/hr, n = 27) and group 5 (100-160 cGy/hr, n = 13). The local failure rate was significantly increased in the group of patients treated with implant dose-rate < 30 cGy/hr (p < 0.05). While the incidence of late normal tissue complications and poor cosmetic outcome was significantly higher in the group of patients treated with implant dose-rate > 100 cGy/hr (p < 0.05). CONCLUSION The present analysis indicate that the implant dose-rate should be maintained between 30-70 cGy/hr to maximize local control and reduce the late normal tissue injury. Also the increase in dose per fraction of external irradiation while not influencing local control rate was crucial for incidence of late complications and cosmetic outcome.

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.

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.

Dosimetric evaluation of rectum and bladder using image-based CT planning and orthogonal radiographs with ICRU 38 recommendations in intracavitary brachytherapy

The purpose is to compare CT-based dosimetry with International Commission on Radiation Units and Measurements (ICRU 38) bladder and rectum reference points in patients of carcinoma of uterine cervix treated with intracavitary brachytherapy (ICA). Twenty-two consecutive patients were evaluated. Orthogonal radiographs and CT images were acquired and transferred to PLATO planning system. Bladder and rectal reference points were identified according to ICRU 38 recommendations. Dosimetry was carried out based on Manchester system. Patient treatment was done using 192Iridium high dose rate (HDR) remote after-loading machine based on the conventional radiograph-based dosimetry. ICRU rectal and bladder point doses from the radiograph plans were compared with D2, dose received by 2 cm3 of the organ receiving maximum dose from CT plan. V2, volume of organ receiving dose more than the ICRU reference point, was evaluated. The mean (±standard deviation) volume of rectum and bladder was 60 (±28) cm3 and 138 (±41) cm3 respectively. The mean reference volume in radiograph and CT plan was 105 (±7) cm3 and 107 (±7) cm3 respectively. It was found that 6 (±4) cm3 of rectum and 16 (±10) cm3 of bladder received dose more than the prescription dose. V2 of rectum and bladder was 7 (±1.7) cm3 and 20.8 (±6) cm3 respectively. Mean D2 of rectum and bladder was found to be 1.11 (±0.2) and 1.56 (±0.6) times the mean ICRU reference points respectively. This dosimteric study suggests that comparison of orthogonal X-ray-based and CT-based HDR ICA planning is feasible. ICRU rectal point dose correlates well with maximum rectal dose, while ICRU bladder point underestimates the maximum bladder dose.

Predictive role of tdf values in late rectal recto-sigmoid complications in irradiation treatment of cervix cancer

Radiation-induced late rectal and recto-sigmoid complications for different doses per fraction were analyzed retrospectively in 203 cases of Stage IIIB carcinoma of the uterine cervix. The patients were treated with a combination of external irradiation and a single intracavitary insertion during January 1979 to December 1983. The external irradiation was randomised to deliver by four different fractionation regimens having dose per fraction of 2 Gy, 3 Gy, 4 Gy and 5.4 Gy. The doses for various fractionations were matched with the daily regimen using the time-dose factors (TDF) model. A single intracavitary insertion delivered a dose of 22 to 24 Gy to point A using Fletcher-Suit applicator. All patients had a minimum follow-up of 30 months. Thirty nine cases of late radiation induced rectal and recto-sigmoid complications were observed. The complication rate of 8.2% for daily treatment regimen delivering 2 Gy per fraction was increased to 33.3% for once weekly treatment regimen delivering 5.4 Gy per fraction (p = 0.041). Despite similar Time-Dose Factors (TDF) values in four different treatment regimens, the complication rate increased significantly in the once weekly regimen. The analysis suggest that the Time-Dose Factors (TDF) values do not predict correctly the late normal tissue reactions for different dose fractionation schedules.

Impact of radiation dose on locoregional control and survival on squamous cell carcinoma of anal canal

PURPOSE To perform a systematic analysis of clinical data of presentation, treatment, outcome, toxicity, survival and other associated prognostic factors of the patients of anal canal who received treatment at our hospital. METHODS AND MATERIALS The medical records of 257 patients treated with radiotherapy with or without chemotherapy from the year 1985 to 2005 were studied. RESULTS Median follow-up was 36months. Complete clinical response after radiotherapy was 74.4% in the whole group. The 5years overall (OAS) and disease-free (DFS) survival for the whole group was 71.5% and 61%, respectively. Patients with T1-2 tumors which received the radiation dose between 55 and 60Gy had superior locoregional control, DFS and OAS. Similarly T3-4 tumors receiving radiation dose more than 60Gy independently improved the locoregional control, DFS and OAS irrespective of the nodal status and addition of chemotherapy. CONCLUSIONS Radiation dose of 56-60Gy for T1 and T2 and 65Gy for T3 and T4 tumors along with concurrent chemotherapy is required to achieve better local control, disease-free survival and overall survival, with acceptable toxicity.

Comparison of 2 contouring methods of bone marrow on CT and correlation with hematological toxicities in non-bone marrow-sparing pelvic intensity-modulated radiotherapy with concurrent cisplatin for cervical cancer.

Objectives To compare volumes and dose volume histogram (DVH) parameters for bone marrow contours using 2 methods on computed tomography (CT) and correlation with grade 2 or higher hematological toxicity (HT) in patients with cervical cancer treated with non–bone marrow–sparing intensity-modulated radiotherapy (IMRT) with concurrent cisplatin. Materials and Methods The planning CT scans of 47 patients prospectively enrolled and treated with IMRT arm of a phase 2 trial (NCT00193804) contoured for pelvic bone marrow in 2 sets; whole bone (WB), and freehand (FH) inner cavity of bone. Various subvolumes were made in each set—sacrum, ilium, ischium, lower pelvis, lumbosacral spine, sacrum, and whole pelvis—and compared for volume and DVH parameters (V10, V20, V30, and V40) using paired t test. The hematological parameters during RT compiled from electronic database analyzed for higher than grade 2 (Radiation Therapy Oncology Group) HT and correlated with DVH parameters using log regression analysis (P < 0.05 significant). Results The FH subvolumes were 25% to 30% of WB. The mean DVH parameters V10, V20, V30, and V40 for whole-pelvis FH and WB were 86.5%, 77.5%, 62.5%, and 40.5%; and 88%, 79.6%, 62.9%, and 40%, respectively. There was significant difference between the DVH parameters of 2 sets (P < 0.05) for all subvolumes except ischium V20, sacrum V10, and lumbosacral spine V10. The leukopenia, neutropenia, anemia, and thrombocytopenia higher than grade 2 was seen in 53%, 29.8%, 65.9%, and 10.6%, respectively. The mean V10 for whole pelvis was less than 90% for both sets. On both univariate and multivariate analyses, only FH whole pelvis V40 more than or equal to 40% correlated with higher than grade 2 leukopenia (Mann-Whitney U test, P = 0.026) and neutropenia (P = 0.05) with odds ratio, 4 (95% confidence interval, 1.166–13.728; P = 0.028). Conclusions The FH bone marrow cavity volume is a better surrogate of active bone marrow on CT images and correlated with higher than grade 2 HT (V40 >40%). Further prospective studies validating significance of high-dose effects and identifying correlation of bioimaging with CT contouring are warranted.

Brachytherapy in India - a long road ahead.

Brachytherapy can play a very important role in the definitive cure by radiation therapy in India. However, except for in a handful of centres, the majority of hospitals use it only for intracavitary treatment. The most probable reasons for such are the lack of logistical resources in terms of trained personal and supporting staff, rather than lack of radiotherapy machines and equipment. In this article, the authors look into the various aspects of brachytherapy in India: from its beginning to present days. The authors point out the resources available, shortcomings, and some possible solutions to make use of brachytherapy more popular and effective. Apart from presenting a picture of the present scenario, the article pays attention to the positive signs of brachytherapy becoming more popular in the near future.

Treatment and outcome in cancer cervix patients treated between 1979 and 1994: A single institutional experience

INTRODUCTION A retrospective review in patients with carcinoma cervix to evaluate the changes and trends in demographics, evolution of protocols, and outcome analysis over 16 years. MATERIALS AND METHODS This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed. RESULTS With a mean age of 46 years (range: 18-90 years; median: 45 years), 669 (11%) patients were in stage Ib, 284 (5%) were in stage IIa, 1891 (30%) were in stage IIb, 69 (1%) were in stage IIIa, and 3321 (53%) were in stage IIIb. With a median follow-up of 68 months (57-79 months) for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO) Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT) + Sx or after radical radiation; their disease-free survival (DFS) was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years. CONCLUSION Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.

Whole abdomen radiation therapy in ovarian cancers: a comparison between fixed beam and volumetric arc based intensity modulation.

PurposeA study was performed to assess dosimetric characteristics of volumetric modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT) for Whole Abdomen Radiotherapy (WAR) after ovarian cancer.Methods and MaterialsPlans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the whole abdomen (PTV_WAR) and 45 Gy to the pelvis and pelvic nodes (PTV_Pelvis) with Simultaneous Integrated Boost (SIB) technique. Plans were investigated for 6 MV (RA6, IMRT6) and 15 MV (RA15, IMRT15) photons. Objectives were: for both PTVs V90% > 95%, for PTV_Pelvis: Dmax < 105%; for organs at risk, maximal sparing was required. The MU and delivery time measured treatment efficiency. Pre-treatment Quality assurance was scored with Gamma Agreement Index (GAI) with 3% and 3 mm thresholds.ResultsIMRT and RapidArc resulted comparable for target coverage. For PTV_WAR, V90% was 99.8 ± 0.2% and 93.4 ± 7.3% for IMRT6 and IMRT15, and 98.4 ± 1.7 and 98.6 ± 0.9% for RA6 and RA15. Target coverage resulted improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV_WAR was 0.34 ± 0.05 and 0.32 ± 0.06 (IMRT6 and IMRT15), 0.30 ± 0.03 and 0.26 ± 0.04 (RA6 and RA15); for PTV_Pelvis, it resulted equal to 0.1 for all techniques. For organs at risk, small differences were observed between the techniques. MU resulted 3130 ± 221 (IMRT6), 2841 ± 318 (IMRT15), 538 ± 29 (RA6), 635 ± 139 (RA15); the average measured treatment time was 18.0 ± 0.8 and 17.4 ± 2.2 minutes (IMRT6 and IMRT15) and 4.8 ± 0.2 (RA6 and RA15). GAIIMRT6 = 97.3 ± 2.6%, GAIIMRT15 = 94.4 ± 2.1%, GAIRA6 = 98.7 ± 1.0% and GAIRA15 = 95.7 ± 3.7%.ConclusionRapidArc showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.