Anusheel Munshi

Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

PURPOSE To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). METHODS AND MATERIALS Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. RESULTS Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. CONCLUSION Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

Weight loss during radiotherapy for head and neck malignancies: what factors impact it?

Radiotherapy (RT) is an important treatment modality in head and neck cancers. Loss of weight during RT due to various factors is a matter of concern. This study was conducted to see the pattern of weight loss and the causative factors involved. One hundred forty patients with head and neck cancer treated with radical RT, concurrent chemoradiation, or postoperative RT were retrospectively studied. A dose of 70 Gy was given in the radical and in the chemoradiation schedule. In postoperative RT, a dose of 60-64 Gy was delivered. During the weekly review of the patients, serial recording of their weight was done along with measurement of other parameters. Analysis was done to see which factors were causative in patients having a weight loss of >5 kg and of >10%. Three variables were found to be significant for the >5-kg weight loss. These were a low initial Karnofsky performance score (KPS; <0.001), use of chemoradiation (P < 0.001), and a total dose of >60 Gy (P = 0.04). For the >10% weight loss, the significant factors were low initial KPS (P < 0.001) and use of chemoradiation (P < 0.001). Therefore, it is important to take care of the nutrition of those patients who have a low KPS, are on chemoradiation, or will be delivered a dose of >60 Gy. The role of prophylactic Ryles tube placement or agents such as megestrol acetate in such patients should be further investigated.

Prospective Evaluation of Radiotherapy With Concurrent and Adjuvant Temozolomide in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

PURPOSE To present outcome data in a prospective study of radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in children with diffuse intrinsic pontine gliomas (DIPGs). METHODS AND MATERIALS Pediatric patients with newly diagnosed DIPGs were prospectively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m(2), Days 1-42). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m(2), Days 1-5) was given every 28 days to a maximum of 12 cycles. Response was evaluated clinically and radiologically with magnetic resonance imaging and positron emission tomography scans. RESULTS Between March 2005 and November 2006, 20 children (mean age, 8.3 years) were accrued. Eighteen patients have died from disease progression, one patient is alive with progressive disease, and one patient is alive with stable disease. Median overall survival and progression-free survival were 9.15 months and 6.9 months, respectively. Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients, leucopenia in 2, and vomiting in 7. Transient Grade II skin toxicity developed in the irradiated fields in 18 patients. During the adjuvant TMZ phase, Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient. Patients with magnetic resonance imaging diagnosis of a high-grade tumor had worse survival than those with a low-grade tumor (p = 0.001). Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not (p = 0.048). CONCLUSIONS TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone. Further clinical trials should explore novel treatment modalities.

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.

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.

Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience

CONTEXT Lung cancer has varied epidemiology depending on the geographic region. Globally, there have been important changes in incidence trends amongst men and women, histology, and incidence in non-smokers. Indian epidemiological data on lung cancer is scarce. AIMS We set out to study the epidemiological patterns and clinical profile of lung cancer in India. MATERIALS AND METHODS We interviewed patients discussed in the thoracic oncology multidisciplinary meetings between 2008 and 2009. Demographic data, smoking history, place of residence, histology, stage at presentation, and treatment details were collected. Data was entered and analyzed in SPSS. RESULTS There were 489 patients, with a median age of 56 years, of which 255 (52%) were non-smokers and 234 (48%) were smokers. One hundred and thirty-three patients had consumed smokeless tobacco. The male-to-female ratio was 3.5:1. Sixty-nine patients (14.1%) were incorrectly diagnosed and treated with anti-tuberculosis treatment, which delayed the diagnosis of lung cancer by four months. Eight percent of patients had small-cell carcinoma; of the 92% patients with non-small-cell carcinoma (NSCLC), the most common histology was adenocarcinoma (43.8%), followed by squamous cell (26.2%), large cell (2.1%) and other (8.3%). Eighteen percent of patients were diagnosed by cytology, therefore were diagnosed as NSCLC, without further histologic subtyping. Most patients (43%) were in Stage III at presentation. Lung followed by bone were the common sites of metastases. The majority of the patients (49%) received palliative chemotherapy. Among definitive therapy, concurrent chemo-radiation (13%) was offered more frequently than surgery (6%). CONCLUSION Considerably higher numbers of Indian patients with lung cancer are non-smokers, compared to the West. The global trend of rise in adenocarcinoma is paralleled in India. Non-tobacco-related risk factors need further investigation.

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.

Radiation Therapy with Implanted Cardiac Pacemaker Devices: a Clinical and Dosimetric Analysis of Patients and Proposed Precautions

AIMS To report the radiation planning dosimetric aspects and clinical outcomes of patients with implanted cardiac pacemakers. MATERIALS AND METHODS Between 2005 and 2009, eight patients with in situ cardiac pacemakers of varied primary site were treated at our hospital. All patients underwent computed tomography-based treatment planning. The target volumes, organs at risk and pacemaker device were all contoured. A treatment plan optimally covering the target area and maximally sparing the pacemaker was generated. All patients were evaluated at baseline, during radiotherapy and after radiotherapy conclusion by a cardiologist as well as pacemaker company personnel. RESULTS The median age at presentation was 67 (range 53-77) years. There were three men with head and neck primaries, two men with lung primaries and three women with breast primaries. The prescribed dose ranged from 45 to 70 Gy in 25-35 fractions with a daily dose of 1.8-2.0 Gy. Four patients had the pacemaker implanted on the same side as the radiotherapy target. The dose ranges for the minimum, mean and maximum doses to the pacemaker were 0.06-2.0, 0.07-20.6 and 0.14-60.0 Gy, respectively. Radiation therapy was safely delivered in all patients without any untoward effects. At 5 months of median follow-up, all patients were well with no malfunction of the pacemaker. CONCLUSION A series of eight patients with in situ pacemakers treated with radiotherapy is reported. Radiotherapy can be safely delivered in patients with implanted cardiac pacemakers. However, it mandates a cautious approach in planning and treatment delivery to ensure the least possible dose to the pacemaker. Close liaison with the cardiologist and a pacemaker clinic before, during and after the course of treatment is essential to ensure patient safety.

Radiation therapy planning of a breast cancer patient with in situ pacemaker–challenges and lessons

A postmenopausal lady with an in situ pacemaker developed a lump in the left breast and was diagnosed to have breast cancer. The patient underwent breast conservative surgery and was planned for post operative radiotherapy. The location of the tumor relative to the pacemaker provided a unique challenge in planning radiotherapy and the patient had an uneventful post radiotherapy course. A literature review revealed that modern generation pacemakers are very sensitive to radiation compared to their older counterparts. The present article makes suggestions towards reducing dose in radiotherapy planning in pacemaker patients.

Encouraging experience of concomitant Temozolomide with radiotherapy followed by adjuvant Temozolomide in newly diagnosed glioblastoma multiforme: single institution experience

The purpose of this study was to report our experience with concomitant and adjuvant temozolomide (TMZ) with radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Forty-two newly diagnosed histopathologically proven patients with GBM underwent maximal safe resection followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks along with concomitant oral TMZ (75 mg/m2) daily followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Patients were 13 – 69 years of age with a median age of 49.5 years (31 males, 11 females). Fifty per cent of patients underwent a gross total resection of tumour, 43% had partial resection, and 7% an open or stereotactic biopsy only. 53% of the patients had a post-operative Karnofsky Performance Score (KPS) of 60 – 80%. All patients received concomitant radiation and TMZ with 74% of the patients completing six cycles of adjuvant TMZ. At a median follow-up of 12.5 months, the 1- and 2-year survival was 67 and 29%, respectively. The median overall and progression-free survival was 16.4 and 14.9 months respectively. Patients with pretreatment KPS of >80% had significantly better overall survival as compared with those having KPS ≤80% (median survival 22.12 vs. 11.97 months; p = 0.026). Treatment was generally well tolerated with 9% of patients developing grade 3 anaemia, 2% grade 3 leucopoenia, and 7% patients grade 3 or 4 thrombocytopenia respectively during the treatment. At last follow-up, among the surviving patients, 30% had a maintained KPS greater than 90%. Concomitant radiotherapy and TMZ followed by adjuvant TMZ prolongs survival in patients with glioblastoma multiforme and is well tolerated in our patient population.