Ashwini Budrukkar

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.

Factors Influencing Cosmetic Outcome in Breast Conservation

With more than 1 million new cases each year, female breast cancer is the second most common cancer in the world and the most common cancer among women. Breast cancer involves a multimodality treatment and a co-ordinated approach from various specialties. Breast-conserving therapy (BCT) is increasingly being integrated into the management of breast cancer. The obvious advantages of BCT are equivalent local and distant control rates as compared with mastectomy and the preservation of the breast. However, the key to a successful BCT is achieving a cosmetic outcome that is acceptable to the patient and the physician. Cosmesis in breast cancer is the end result of a range of factors that fall under the broad heads of surgery, radiotherapy, chemotherapy and hormonal treatment. All of these modalities can play a role in compromising breast cosmesis. This overview discusses the factors that are critical in affecting the final cosmetic outcome in patients with BCT.

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.

Management of locally advanced breast cancer: Evolution and current practice

Locally advanced breast cancer (LABC) accounts for a sizeable number (30-60%) of breast cancer cases and is a common clinical scenario in developing countries. The treatment of LABC has evolved from single modality treatment, consisting of radical mutilating surgery or higher doses of radiotherapy in inoperable disease to multimodality management, which along with the above two included systemic therapy. Neoadjuvant chemotherapy (NACT) has made a tremendous impact on the management of LABC. NACT was initiated to institute systemic therapy upfront at the earliest in this group of patients with a high risk of micrometastasis burden. While NACT did not yield a survival advantage, it has however made breast conservation possible in selected group of cases. Large number of studies and many randomised trials have been done in women with LABC in order to improve the therapeutic decisions and also the local control and survival. With this background we have reviewed various treatment options in patients with LABC which should possibly help in guiding the clinicians for optimal management of LABC.

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.

Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer

Background Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images. Methods hNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images. Results Staining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p = 0.0033, CI = 95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2–ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method. Conclusion The study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted 131I radio-ablative therapy is aimed.

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.

Breast Radiation Therapy Guideline Implementation in Low- and Middle-Income Countries

Radiation therapy plays a critical role in the management of breast cancer and often is unavailable to patients in low‐ and middle‐income countries (LMCs). There is a need to provide appropriate equipment and to improve the techniques of administration, quality assurance, and use of resources for radiation therapy in LMCs. Although the linear accelerator is the preferred equipment, telecobalt machines may be considered as an acceptable alternative in LMCs. Applying safe and effective treatment also requires well trained staff, support systems, geographic accessibility, and the initiation and completion of treatment without undue delay. In early‐stage breast cancer, standard treatment includes the irradiation of the entire breast with an additional boost to the tumor site and should be delivered after treatment planning with at least 2‐dimensional imaging. Although postmastectomy radiation therapy (PMRT) has demonstrated local control and overall survival advantages in all patients with axillary lymph node metastases, preference in limited resource settings could be reserved for patients who have ≥4 positive lymph nodes. The long‐term risks of cardiac morbidity and mortality require special attention to the volume of heart and lungs exposed. Alternative treatment schedules like hypofractionated radiation and partial breast irradiation currently are investigational. Radiation therapy is an integral component for patients with locally advanced breast cancer after initial systemic treatment and surgery. For patients with distant metastases, radiation is an effective tool for palliation, especially for bone, brain, and soft tissue metastases. The implementation of quality‐assurance programs applied to equipment, the planning process, and radiation treatment delivery must be instituted in all radiation therapy centers. Cancer 2008;113(8 suppl):2305–14.

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.