Shyam Kishore Shrivastava

A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy

PURPOSE A treatment planning study was performed to evaluate the performance of the novel volumetric modulated single arc radiotherapy on cervix uteri cancer patients. Conventional fixed field IMRT was used as benchmark. METHODS AND MATERIALS CT datasets of eight patients were included in the study. Plans were optimised with the aim to assess organs at risk and healthy tissue sparing while enforcing highly conformal target coverage. Planning objectives for PTV were: maximum significant dose lower than 52.5 Gy and minimum significant dose higher than 47.5 Gy. For organs at risk, the median and maximum doses were constrained to be lower than 30 (rectum), 35 (bladder) and 25 Gy (small bowel) and 47.5 Gy; additional objectives were set on various volume thresholds. Plans were evaluated on parameters derived from dose volume histograms and on NTCP estimates. Peripheral doses at 5, 10 and 15 cm from the PTV surface were recorded to assess the low-level dose bath. The MU and delivery time were scored to measure expected treatment efficiency. RESULTS Both RapidArc and IMRT resulted in equivalent target coverage but RapidArc had an improved homogeneity (D(5%)-D(95%) = 3.5 +/- 0.6 Gy for RapidArc and 4.3 +/- 0.8 Gy for IMRT) and conformity index (CI(90%) = 1.30 +/- 0.06 for RapidArc and 1.41 +/- 0.15 for IMRT). On rectum the mean dose was reduced by about 6 Gy (10 Gy for the rectum fraction not included in the PTV). Similar trends were observed for the various dose levels with reductions ranging from approximately 3 to 14.4 Gy. For the bladder, RapidArc allowed a reduction of mean dose ranging from approximately 4 to 6Gy and a reduction from approximately 3 to 9 Gy w.r.t. IMRT. Similar trends but with smaller absolute differences were observed for the small bowel and left and right femur. NTCP calculations on bladder and rectum confirmed the DVH data with a potential relative reduction ranging from 30 to 70% from IMRT to RapidArc. The healthy tissue was significantly less irradiated in the medium to high dose regions (from 20 to 30 Gy) and the integral dose reduction with RapidArc was about 12% compared to IMRT. Concerning peripheral dose, the relative difference between IMRT and RapidArc was of 9 +/- 2%, 43 +/- 11% and 36 +/- 5% at 5, 10 and 15 cm from the PTV surface, respectively. The MU/Gy from RapidArc was 245 +/- 17 corresponding to an expected average beam on time of 73 +/- 10 s per fractions of 2 Gy. IMRT plans presented higher values with an average of MU/Gy = 479 +/- 63. CONCLUSION RapidArc was investigated for cervix uteri cancer showing significant improvements in organs at risk and healthy tissue sparing with uncompromised target coverage leading to better conformal avoidance of treatments w.r.t. conventional IMRT. This, in combination with the confirmed short delivery time, can lead to clinically significant advances in the management of this highly aggressive cancer type. Clinical protocols are now advised to evaluate prospectively the potential benefit observed at the planning level.

Volumetric modulated arc radiotherapy for carcinomas of the oro-pharynx, hypo-pharynx and larynx: A treatment planning comparison with fixed field IMRT

PURPOSE A planning study was performed to evaluate the performance of volumetric modulated arc radiotherapy on head and neck cancer patients. Conventional fixed field IMRT was used as a benchmark. METHODS AND MATERIALS CT datasets of 29 patients with squamous cell carcinoma of the oro-pharynx, hypo-pharynx and larynx were included. Plans for fixed beam IMRT, single (RA1) and double (RA2) modulated arcs with the RapidArc technique were optimised. Dose prescription was set to 66 Gy to the primary tumour (at 2.2 Gy/fraction), 60 Gy to intermediate-risk nodes and 54 Gy to low-risk nodal levels. The planning objectives for PTV were minimum dose >95%, and maximum dose <107%. Maximum dose to spinal cord was limited to 46 Gy, maximum to brain stem to 50 Gy. For parotids, mean dose <26 Gy (or median <30 Gy) was assumed as the objective. The MU and delivery time were scored to measure expected treatment efficiency. RESULTS Target coverage and homogeneity results improved with RA2 plans compared to both RA1 and IMRT. All the techniques fulfilled the objectives on maximum dose, while small deviations were observed on minimum dose for PTV. The conformity index (CI(95%)) was 1.7+/-0.2 for all the three techniques. RA2 allowed a reduction of D(2%) to spinal cord of approximately 3 Gy compared to IMRT (RA1 D(2%) increased it of approximately 1 Gy). On brain stem, D(2%) was reduced from 12 Gy (RA1 vs. IMRT) to 13.5 Gy (RA2 vs. IMRT). The mean dose to ipsi-lateral parotids was reduced from 40 Gy (IMRT) to 36.2 Gy (RA1) and 34.4 Gy (RA2). The mean dose to the contra-lateral gland ranged from 32.6 Gy (IMRT) to 30.9 Gy (RA1) and 28.2 Gy (RA2). CONCLUSION RapidArc was investigated for head and neck cancer. RA1 and RA2 showed some improvements in organs at risk and healthy tissue sparing, while only RA2 offered improved target coverage with respect to conventional IMRT.

THERAPEUTIC FACTORS INFLUENCING THE COSMETIC OUTCOME AND LATE COMPLICATIONS IN THE CONSERVATIVE MANAGEMENT OF EARLY BREAST CANCER

PURPOSE To investigate the impact of clinical and physical parameters on the cosmetic result and complications, in cancer breast treated with conservative surgery and definitive irradiation. METHODS AND MATERIALS Between October 1980 and December 1990, 289 patients were treated with lumpectomy and/or axillary dissection, radical irradiation with or without adjuvant therapy. The radiation therapy technique consisted of external beam therapy followed by an Ir-192 implant or electron beam boost. Univariate and multivariate analysis were used to evaluate the correlation between multiple factors affecting the cosmetic outcome and the complications. RESULTS Of 289 patients, cosmesis was evaluable in 285 and recorded as excellent to good in 226 (79%), fair in 35 (12%), and poor in 24 (9%). On multivariate analysis of these results, a high dose per fraction (p = .0018), and use of electrons as boost to the tumor bed (p = .001) were found to be significant. When patients boosted with electrons were excluded, a high boost dose (p = .0433) was also found significant. Fifteen (5%) patients developed severe late radiation sequelae and 14 (5%) moderate or severe arm edema. On multivariate analysis only dose per fraction of 2.5 Gy (p < .0001) and higher boost doses (p = .017) were significant. CONCLUSION In 289 patients of early breast cancer treated with conservative surgery and radical irradiation, multivariate analysis suggests that higher dose per fraction with teletherapy and higher brachytherapy boost dose adversely affect cosmesis and contribute to the late complications.

Primary Diffuse Large B-Cell Lymphoma of the Tonsil Is a Higher Radiotherapy Dose Required?

The purpose was to evaluate the prognostic factors and treatment outcome of Indian patients with primary diffuse large B‐cell lymphoma (DLBCL) of the tonsil treated at a single institution.

Volumetric Modulation Arc Radiotherapy With Flattening Filter-Free Beams Compared With Static Gantry IMRT and 3D Conformal Radiotherapy for Advanced Esophageal Cancer: A Feasibility Study

PURPOSE A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RESULTS RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). CONCLUSION RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time.

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.

Osteosarcoma of the head and neck region: Lessons learned from a single-institution experience of 50 patients

Osteosarcoma of the head and neck region is a rare tumor and is a therapeutic challenge because of its aggressive nature and complex anatomical location. Standard management guidelines are lacking due to paucity of published data.

HPV Genotyping and Site of Viral Integration in Cervical Cancers in Indian Women

Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270) from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63%) followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86) and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal) could be an important prognostic marker for cervical cancer.

Factors affecting the quality of voice in the early glottic cancer treated with radiotherapy.

AIMS To prospectively analyze the objective voice quality before and after radiotherapy (RT) for early glottic cancer and to evaluate the role of different factors that may affect it. METHODS Patients with T1-T2N0M0 glottic cancer underwent voice quality assessment before treatment and after radical RT. Post-RT voice quality was compared to the voice at diagnosis and the voice of healthy individuals used as controls. A comprehensive set of voice parameters were measured. The effects of age, smoking history, T stage, anterior commissure (AC) involvement, radiation dose, fractionation and volumes on pre-treatment and post-treatment voice quality were analyzed. RESULTS The voice quality data of 50 patients were analyzed. Following treatment, there was a significant improvement in the majority of measured parameters. However, perturbation and HNR remained inferior compared to controls. A history of smoking, AC involvement and larger RT volumes resulted in poorer voice parameters following RT. There was no significant impact of age alone. T2 tumors had an inferior voice quality before treatment, but did not remain inferior following RT. Hypofractionated RT did not show any negative impact. CONCLUSIONS There is a considerable improvement of voice quality following RT. Several factors may have specific effects on pre-treatment and post-treatment voice.

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.