Jamema Swamidas

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.

Late rectal toxicity after image-based high-dose-rate interstitial brachytherapy for postoperative recurrent and/or residual cervical cancers: EQD2 predictors for Grade

PURPOSE To investigate the correlation of rectal dose volume metrics with late rectal toxicity after high-dose-rate pelvic interstitial brachytherapy. METHODS AND MATERIALS From October 2009 to November 2012, 50 patients with residual or recurrent cervical cancer were included. Patients received external radiation 50 Gy in 25 fractions over 5 weeks with weekly cisplatin. Rectum and rectal mucosal (RM) contours were delineated retrospectively. RM was defined as the outer surface of the flatus tube inserted at brachytherapy. The dose received by 0.1, 1, 2, 5 cc of rectum, RM, and sigmoid was recorded. Cumulative equivalent dose in 2 Gy (EQD2) for organs at risk was calculated assuming α/β of 3. Univariate analysis was performed to identify predictors of rectal toxicity. RESULTS At a median follow-up of 34 months (12-51 months), Grade II and III late rectal toxicity was observed in 9 (18%) and 2 (4%) patients, respectively. On univariate analysis, rectal doses were not significant predictors; however, D 0.1-cc RM dose >72 Gy (p = 0.04), D 1-cc RM dose >65 Gy (p = 0.004), D 2-cc RM dose >62.3 Gy (p = 0.004), and D 5-cc RM dose >60 Gy (p = 0.007) correlated with Grade ≥II toxicity. On probit analysis, the estimated dose in EQD2 for a 10% and 20% risk of rectal toxicity was D 2-cc rectum of 55 and 66 Gy, and RM <55 and 63 Gy, respectively. CONCLUSIONS Limiting 2-cc RM and rectal doses within the proposed thresholds can minimize Grade ≥II toxicity for gynecologic high-dose-rate interstitial brachytherapy.

II toxicity

BACKGROUND AND PURPOSE This study evaluates the impact of MRI guided adaptive brachytherapy (BT) on uterine corpus dose. MATERIAL AND METHODS 84 patients with median follow-up of 18 months were analysed. MRI based BT was done according to GEC-ESTRO guidelines. Non-involved uterine corpus at the time of BT was contoured and the uterine corpus dose (D90 and D98) was evaluated for (1) standard loading pattern with source loading to the tip of the tandem and (2) optimised dose plan. Tandem lengths and heights of the 85 Gy isodose were recorded. RESULTS Dose optimisation resulted in a reduction of active tandem length of 0.4±0.4 cm leading to lowering the D90 to the non-involved uterine corpus from 63.8±9.5 Gy to 56.7±7.5 Gy EQD2 (p<0.0001). Mean active tandem length was 5.0±1.0 cm, and the height of the 85 Gy isodose was 5.7±1.0 cm in optimised plans. CONCLUSIONS MRI guided dose optimisation lowered the dose to the uterine corpus. However, a total EBRT+BT dose larger than 50 Gy was obtained in 99% of patients. Assuming that 45-50 Gy is sufficient to eradicate microscopic disease, the lowering of uterus corpus dose is not expected to induce additional uterine corpus recurrences in the setting of MRI guided adaptive BT. This hypothesis should be tested in a larger number of patients as e.g. the EMBRACE study.

Dose to the non-involved uterine corpus with MRI guided brachytherapy in locally advanced cervical cancer

BACKGROUND AND PURPOSE Recently, a vaginal dose reporting method for combined EBRT and BT in cervical cancer patients was proposed. The current study was to evaluate vaginal doses with this method in a multicentre setting, wherein different applicators, dose rates and protocols were used. MATERIAL AND METHODS In a subset of patients from the EMBRACE study, vaginal doses were evaluated. Doses at the applicator surface left/right and anterior/posterior and at 5mm depth were measured. In addition, the dose at the Posterior-Inferior Border of Symphysis (PIBS) vaginal dose point and PIBS±2cm, corresponding to the mid and lower vagina, was measured. RESULTS 153 patients from seven institutions were included. Large dose variations expressed in EQD2 with α/β=3Gy were seen between patients, in particular at the top left and right vaginal wall (median 195 (range 61-947)Gy/178 (61-980)Gy, respectively). At 5mm depth, doses were 98 (55-212)Gy/91 (54-227)Gy left/right, and 71 (51-145)Gy/67 (49-189)Gy anterior/posterior, respectively. The dose at PIBS and PIBS±2cm was 41 (3-81)Gy, 54 (32-109)Gy and 5 (1-51)Gy, respectively. At PIBS+2cm (mid vagina) dose variation was coming from BT. The variation at PIBS-2cm (lower vagina) was mainly dependent on EBRT field border location. CONCLUSIONS This novel method for reporting vaginal doses coming from EBRT and BT through well-defined dose points gives a robust representation of the dose along the vaginal axis. In addition, it allows comparison of vaginal dose between patients from different centres. The doses at the PIBS points represent the doses at the mid and lower parts of the vagina. Large variations in dose throughout the vagina were observed between patients and centres.

Multicentre evaluation of a novel vaginal dose reporting method in 153 cervical cancer patients

The adequacy of setup margins for various sites in patients treated with helical tomotherapy was investigated. A total of 102 patients were investigated. The breakdown of the patients were as follows: Twenty-five patients each in brain, head and neck (H and N), and pelvis, while 12 patients in lung and 15 in craniospinal irradiation (CSI). Patients were immobilized on the institutional protocol. Altogether 2686 megavoltage computed tomography images were analyzed with 672, 747, 622, 333, and 312 fractions, respectively, from brain, H and N, pelvis, lung, and CSI. Overall systematic and random errors were calculated in three translational and three rotational directions. Setup margins were evaluated using van Herk formula. The calculated margins were compared with the margins in the clinical use for various directions and sites. We found that the clinical isotropic margin of 3 mm was adequate for brain patients. However, in the longitudinal direction it was found to be out of margin by 0.7 mm. In H and N, the calculated margins were well within the isotropic margin of 5 mm which is in clinical use. In pelvis, the calculated margin was within the limits, 8.3 mm versus 10 mm only in longitudinal direction, however, in vertical and lateral directions the calculated margins were out of clinical margins 11 mm versus 10 mm, and 8.7 mm versus 7.0, mm respectively. In lung, all the calculated margins were well within the margins used clinically. In CSI, the variation was found in the middle spine in the longitudinal direction. The clinical margins used in our hospital are adequate enough for sites H and N, lung, and brain, however, for CSI and pelvis the margins were found to be out of clinical margins.

Setup error analysis in helical tomotherapy based image-guided radiation therapy treatments.

The aim of this study was to evaluate the dose optimization in 3D image based gynecological interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT). Axial CT image data set of 20 patients of gynecological cancer who underwent external radiotherapy and high dose rate (HDR) interstitial brachytherapy using MUPIT was employed to delineate clinical target volume (CTV) and organs at risk (OARs). Geometrical and graphical optimization were done for optimum CTV coverage and sparing of OARs. Coverage Index (CI), dose homogeneity index (DHI), overdose index (OI), dose non-uniformity ratio (DNR), external volume index (EI), conformity index (COIN) and dose volume parameters recommended by GEC-ESTRO were evaluated. The mean CTV, bladder and rectum volume were 137 ± 47cc, 106 ± 41cc and 50 ± 25cc, respectively. Mean CI, DHI and DNR were 0.86 ± 0.03, 0.69 ± 0.11 and 0.31 ± 0.09, while the mean OI, EI, and COIN were 0.08 ± 0.03, 0.07 ± 0.05 and 0.79 ± 0.05, respectively. The estimated mean CTV D90 was 76 ± 11Gy and D100 was 63 ± 9Gy. The different dosimetric parameters of bladder D2cc, D1cc and D0.1cc were 76 ± 11Gy, 81 ± 14Gy, and 98 ± 21Gy and of rectum/recto-sigmoid were 80 ± 17Gy, 85 ± 13Gy, and 124 ± 37Gy, respectively. Dose optimization yields superior coverage with optimal values of indices. Emerging data on 3D image based brachytherapy with reporting and clinical correlation of DVH parameters outcome is enterprizing and provides definite assistance in improving the quality of brachytherapy implants. DVH parameter for urethra in gynecological implants needs to be defined further.

Dose optimization in gynecological 3D image based interstitial brachytherapy using martinez universal perineal interstitial template (MUPIT) -an institutional experience

PURPOSE To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients. MATERIALS AND METHODS 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/β 10 Gy and 3 Gy. RESULTS Median V85 Gy, V75 Gy and V60 Gy EQD210 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD210 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm3), intermediate (25-35 cm3) and large (>35 cm3) CTVHR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A. CONCLUSIONS MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTVHR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT.

Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy

Purpose Recent guidelines recommend magnetic resonance imaging–based brachytherapy (MRBT) for locally advanced cervical cancer. However, its implementation is challenging within the developing world. This article reports the outcomes of patients with locally advanced cervical cancer treated with chemoradiation and point A–based brachytherapy (BT) using x-ray– or computed tomography–based planning. Methods Patients treated between January 2014 and December 2015 were included. Patients underwent x-ray– or computed tomography–based BT planning with an aim to deliver equivalent doses in 2 Gy (EQD2) > 84 Gy10 to point A while minimizing maximum dose received by rectum or bladder to a point or 2 cc volume to < 75 Gy EQD2 and < 90 Gy EQD2, respectively. The impact of known prognostic factors was evaluated. Results A total of 339 patients were evaluated. Median age was 52 (32 to 81) years; 52% of patients had stage IB2 to IIB and 48% had stage III to IVA disease. There was 85% compliance with chemoradiation, and 87% of patients received four or more cycles. Median point A dose was 84 (64.8 to 89.7) Gy. The median rectal and bladder doses were 73.5 (69.6 to 78.4) Gy3 and 83 (73.2 to 90.0) Gy3, respectively. At a median follow-up of 28 (4 to 45) months, the 3-year local, disease-free, and overall survival for stage IB to IIB disease was 94.1%, 83.3%, and 82.7%, respectively. The corresponding rates for stage III to IVA were 85.1%, 60.7%, and 69.6%. Grade III to IV proctitis and cystitis were observed in 4.7% and 0% of patients, respectively. Conclusion This audit demonstrates good 3-year outcomes that are comparable to published MRBT series. Conventional BT with selective use of interstitial needles and MRBT should continue as standard procedures until level-I evidence for MRBT becomes available.

Standard Chemoradiation and Conventional Brachytherapy for Locally Advanced Cervical Cancer: Is It Still Applicable in the Era of Magnetic Resonance–Based Brachytherapy?

OBJECTIVE To report acute hematological toxicity (HT) in patients receiving post-operative bowel sparing intensity-modulated radiotherapy (IMRT) and cisplatin and its dosimetric predictors. METHODS Clinical database of Phase III trial (NCT01279135), that randomized patients to post-operative conformal or intensity modulated radiation therapy, was searched to select patient strata that received bowel sparing IMRT (50 Gy/25#/5 wks) and concurrent cisplatin (40 mg m-2). Pelvic bone marrow (BM) was retrospectively delineated in two sets: whole bone (WB), and freehand (FH) inner cavity of bone. Dose volume histograms (DVH) of BM were obtained. Receiver operating characteristic (ROC) curve identified DVH thresholds that predicted for Grade≥ II HT with highest specificity. Univariate and multivariate analysis was performed. RESULTS Overall 75 patients received concurrent cisplatin. Grades I-V HT was observed in 38.7%, 42.7%, 14.7%, 0%, and 0% patients, respectively. Grade ≥ II leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 26%, 40%, 26.5%, and 1.4% respectively. None of the HT resulted in treatment break. On univariate analysis, whole pelvis+ lumbar FH V30 >55% & V40>35%, whole pelvis WB and FH V40 > 35%, and lower pelvis WB and FH V40 >20% correlated for Grade ≥ II leucopenia and neutropenia. None of the BM dose volume constraints predicted for overall HT or neutropenia on multivariate analysis. CONCLUSION The IMRT arm of NCT01279135 (PARCER study) that employed strict bowel constraints had unintentional but desirable BM sparing. None of the BM subvolume DVH parameters could be validated on multivariate analysis. ADVANCES IN KNOWLEDGE The prospective study reports feasibility of bone marrow sparing with bowel sparing post-operative pelvic IMRT and concurrent chemotherapy for cervical cancer. The present study reports low incidence of hematological and gastrointestinal toxicity during post-operative chemoradiation with IMRT. As both whole bone and freehand pelvis BM contours predicted for HT, hence an easier method of whole bone contouring should continue to be used till further validation of more specific BM subvolumes becomes available. The study results highlight the need for further research into dose volume constraints during post-operative IMRT.