Vedang Murthy

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.

Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: A randomized controlled trial

PURPOSE To compare three-dimensional conformal radiotherapy (3D-CRT) with intensity modulated radiation therapy (IMRT) in curative-intent irradiation of head-neck squamous cell carcinoma (HNSCC). METHODS Previously untreated patients with biopsy-proven squamous carcinoma of oropharynx, larynx, or hypopharynx (T1-3, N0-2b) were randomly assigned using computer-generated permuted-block design to either 3D-CRT or IMRT, with incidence of physician-rated Radiation Therapy Oncology Group (RTOG) grade 2 or worse acute salivary gland toxicity as primary end-point. RESULTS Between 2005 and 2008, 60 patients randomly allocated to either 3D-CRT (n=28 patients) or IMRT (n=32) were included and analyzed on an intention-to-treat basis. The proportion [95% confidence intervals (CI)] of patients with RTOG grade 2 or worse acute salivary gland toxicity was significantly lesser in the IMRT arm [19 of 32 patients (59%, 95%CI: 42-75%)] as compared to 3D-CRT [25 of 28 patients (89%, 95%CI: 72-97%; p=0.009)]. Late xerostomia and subcutaneous fibrosis were also significantly lesser with IMRT. There was significant recovery of salivary function over time in patients treated with IMRT (p-value for trend=0.0036). At 3-years, there were no significant differences in loco-regional control or survival between the two arms. CONCLUSION IMRT significantly reduces the incidence and severity of xerostomia compared to 3D-CRT in curative-intent irradiation of HNSCC.

Hypofractionated, palliative radiotherapy for advanced head and neck cancer.

BACKGROUND A significant proportion of advanced stage head and neck cancer patients are incurable and have a limited life expectancy. This study reports a single institution experience with a hypofractionated radiotherapy regimen for palliation of loco-regionally advanced and incurable HNSCC. MATERIALS AND METHODS Between 2000 and 2005, 110 patients of unresectable HNSCC were treated with a palliative radiotherapy (40Gy in 16 fractions). Distressing symptoms were assessed before treatment. Patients with good objective regression with acceptable toxicity received further escalation of dose till 50Gy. We made three strata to compare symptomatic improvement namely percentage relief <50%, between 50-75% and >75% as compared to baseline. RESULTS Most common baseline distressing complaints were pain in 109 (99%) patients and dysphagia in 97 (88%) patients. Eleven patients (10%) had complete response (CR) and 80 (73%) patients had complete and partial response (PR). At completion of radiotherapy 26%, 57%, and 17% of patients had <50%, 50-75%, and >75% symptomatic relief, respectively. The overall PFS (defined as either complete disappearance of the disease or non-progression in the irradiated field) at 12 months was 55.1% (95% CI, 40.3%-69.9%). On multivariate analysis weight >50kg (p=0.049) and radiotherapy dose of more than 40Gy (p=0.012) were found to be significant for PFS. Acute and late reactions were acceptable. CONCLUSIONS The hypofractionated radiotherapy regimen evaluated is an effective treatment modality for sustained symptoms relief with good response rates and acceptable toxicity.

A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer.

BACKGROUND Prednisolone is widely used as secondary hormonal treatment for castration-resistant prostate cancer (CRPC). We hypothesised that dexamethasone, another corticosteroid, is more active. OBJECTIVE To compare the activity of prednisolone and dexamethasone in CRPC. DESIGN, SETTING, AND PARTICIPANTS This single-centre, randomised, phase 2 trial was performed in 82 men with chemotherapy-naïve CRPC enrolled from 2006 to 2010. INTERVENTION Prednisolone 5mg twice daily versus dexamethasone 0.5mg once daily versus intermittent dexamethasone 8mg twice daily on days 1-3 every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The main end point was prostate-specific antigen (PSA) response rate. Secondary end points included time to PSA progression, radiologic response rate using Response Evaluation Criteria In Solid Tumors (RECIST), and safety. RESULTS AND LIMITATIONS The intermittent dexamethasone arm was dropped after no response was seen in seven patients. By intention to treat, confirmed PSA response was seen in 41% versus 22% for daily dexamethasone versus prednisolone, respectively (p=0.08). In evaluable patients, the PSA response rates were 47% versus 24% for dexamethasone and prednisolone, respectively (p=0.05). Median time to PSA progression was 9.7 mo on dexamethasone versus 5.1 mo on prednisolone (hazard ratio: 1.6; 95% confidence interval, 0.9-2.8). In 43 patients with measurable disease, the response rate by RECIST was 15% and 6% for dexamethasone and prednisolone, respectively (p=0.6). Of 23 patients who crossed over at PSA progression on prednisolone, 7 of the 19 evaluable (37%) had a confirmed PSA response to dexamethasone. Clinically significant toxicities were rare. CONCLUSIONS Dexamethasone may be more active than prednisolone in CRPC. In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone. PATIENT SUMMARY We compared two different steroids used for treating men with advanced prostate cancer. Our results suggest that dexamethasone may be more effective than prednisolone and that both are well tolerated. CLINICAL TRIAL REGISTRY EUDRAC 2005-006018-16.

Mucoepidermoid carcinoma of the parotid gland: Factors affecting outcome

The purpose of this study was to identify the prognostic factors affecting the outcome in patients with mucoepidermoid carcinoma (MEC) of the parotid gland.

Analysis of prognostic factors in 1180 patients with oral cavity primary cancer treated with definitive or adjuvant radiotherapy

INTRODUCTION The present study identifies the prognostic factors influencing oral cancers in a large cohort of patients treated at a single institute. MATERIALS AND METHODS This is an audit of 1180 patients treated from 1990 to 2004 in the service setting with prospective data collection. Patients were treated with radical radiotherapy or were planned for surgery and post operative radiotherapy (PORT). None of the patients received postoperative concurrent chemoradiation. For analysis, patients were divided into Group 1 and Group 2 based on the oral cavity subsite. RESULTS Of the entire cohort, 810 patients had tumors of the Gingivo-alveolo-buccal complex, lip and hard palate (Group 1) and 370 patients had primaries in tongue and floor of mouth (Group 2). Three year locoregional control for the entire cohort was 58%. The three year local control (LC), locoregional control (LRC) and disease free survival (DFS) for PORT group were 74%, 65% and 60%, respectively, with pathological nodal status, perinodal extension and cut margin status showing statistical significance (P <0.001). In the definitive radiotherapy group, the three year LC, LRC and DFS were 34%, 31% and 30%, respectively, with age, T stage, nodal status and stage being significant. Group 1 patients showed significantly better LC, LRC and DFS than Group 2 patients for the entire cohort. CONCLUSION The results indicate superior outcomes with PORT particularly in advanced stages of oral cancer and inferior outcomes in tongue and floor of mouth subsites. There is scope for improving outcomes by adopting treatment intensification strategies.

Medical decompressive therapy for primary and metastatic intracranial tumours

Medical decompressive therapy (MDT) with corticosteroids and mannitol is often used in patients with primary or metastatic brain tumours. This review highlights the lack of sound evidence regarding the indications and dosage schedule of steroids, prolonged use of which may cause debilitating complications. The available evidence supports the short-term use of MDT for raised intracranial pressure or progressive neurological deficits, but in the absence of these symptoms, MDT is not recommended for stable focal deficits, abnormal higher mental functions, seizures, or as prophylaxis during cranial irradiation. A practical stepladder guideline (based on symptom severity) is proposed with a starting daily dexamethasone dose of 6 mg for non-severe headache and or vomiting; 12 mg for progressive focal neurological deficit with or without non-severe headache or vomiting; and 24 mg dexamethasone with mannitol for severe headache, vomiting, or altered consciousness. Depending on the clinical response, dose can be increased to the next step(s) or tapered every 48 h (more slowly in patients who are dependent on steroids). A scheme for the assessment of efficacy and toxicity prevention is also proposed. The proposed guidelines may be used as a template for further clinical research.

Helical tomotherapy for head and neck squamous cell carcinoma: Dosimetric comparison with linear accelerator-based step-and-shoot IMRT

BACKGROUND Linear Accelerator-based Intensity Modulated Radiation Therapy (IMRT), either as step-and shoot (SS) or in dynamic mode, is now considered routine in the definitive management of head and neck squamous cell carcinoma (HNSCC). Helical TomoTherapy (HT) is a new platform to deliver IMRT. This study aims to compare step-and-shoot Intensity Modulated Radiation Therapy (SS IMRT) with dynamic Helical TomoTherapy (HT) dosimetrically in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS Twelve patients with HNSCC, previously treated with SS IMRT, were re-planned on HT using the same CT dataset. Plans were compared for target coverage and organs-at-risk (OARs) sparing. Sparing of parotids was assessed after stratifying for side (contralateral vs. ipsilateral) and site of disease (laryngopharynx vs. oropharynx). Normal tissue complication probabilities (NTCP) were also compared for the parotid glands. RESULTS All HT plans showed improvement in target coverage and homogeneity, and reduction in OAR doses as compared to SS IMRT plans. For PTV 66, the mean V 99 improved by 14.65% ( P = 0.02). Dose Homogeneity (D 10-90 ) was significantly better in the HT plans (mean 2.07Gy as compared to 4.5Gy in the SS IMRT plans, P = 0.02). HT resulted in an average reduction of mean parotid dose of 12.66Gy and 18.28Gy for the contralateral and ipsilateral glands ( P = 0.003) respectively. This translated into a 24.09% and 35.22% reduction in Normal Tissue Complication Probability (NTCP) for the contralateral and ipsilateral parotids respectively ( P < 0.01). Site of disease (laryngopharynx vs. oropharynx) did not have any significant impact on parotid sparing between SS IMRT and HT. The maximum dose to the spinal cord showed a mean reduction of 12.07Gy in HT plans ( P = 0.02). CONCLUSION Helical Tomotherapy achieved better target coverage with improved OAR sparing as compared to SS IMRT. The significant reduction in mean parotid doses translated into meaningful reduction in NTCP, with potential clinical implications in terms of reduction in Xerostomia and improved quality of life in patients with HNSCC.

Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: a phase II study.

PURPOSE To confirm the efficacy of low-dose involved-field radiation therapy (LD-IFRT) as palliative treatment in patients symptomatic from advanced lymphoma. PATIENTS AND METHODS A total of 36 patients (47 sites), received 4 Gy in 2 fractions to the lymphoma with a 1.5-2-cm margin. Pathology subtypes included 29 (62%) sites with indolent lymphoma and 18 (36%) sites with aggressive lymphoma histology. Bulky disease was seen in 22 (48%) sites and, of these, 6 sites had disease > 10 cm. A median of 3 previous chemotherapy regimens (range, 0 to 9 regimens) preceded LD-IFRT. The primary endpoint of the study was in-field lymphoma control. Patients completed the European Organization for the Research and Treatment of Cancer QLQ-C30 quality of life (QOL) questionnaire before RT and at 3-4 weeks after treatment. RESULTS The overall response rate (RR) at 1-3 months after the RT was 75%. A complete remission (CR) was observed in 13 patients (36%) lasting up to a maximum of 31.3 months and ongoing at analysis. A partial remission (PR) was achieved in 14 patients (39%) lasting up to 10 months. The response rate for non-diffuse large B-cell lymphoma (DLBCL) sites was 86%, while it was 50% for sites with DLBCL histology. Median time to local progression for the entire group was 15 months. There was no statistical difference between the QOL before and after LD-IFRT. CONCLUSION LD-IFRT is an effective and easy treatment for patients with advanced lymphoma that can be repeated at previously irradiated sites, a particularly useful attribute because of the relapsing nature, especially of advanced follicular subtypes.

Recovery of serum testosterone after neoadjuvant androgen deprivation therapy and radical radiotherapy in localized prostate cancer

To prospectively evaluate the time‐course of recovery of serum testosterone levels after a short course of luteinizing hormone‐releasing hormone analogue (LHRHa) and radical radiotherapy to the prostate.