Clinical outcome of patients with primary gliosarcoma treated with concomitant and adjuvant temozolomide: A single institutional analysis of 27 cases.

CONTEXT AND AIM: The prognosis of primary gliosarcoma (PGS) remains dismal with current treatment modalities. We analyzed the outcome of PGS patients treated with concurrent and adjuvant temozolomide (TMZ). SETTINGS AND DESIGN: Retrospective single institutional analysis. MATERIALS AND METHODS: We retrospectively evaluated 27 patients of PGS treated with radiotherapy (RT) and TMZ during 2007‑2012. STATISTICAL ANALYSIS USED: Overall survival (OS) was estimated by the use of Kaplan Meier method and toxicities were evaluate using common terminology criteria for adverse events version 2.0 (National Cancer Institute, USA). RESULTS: Median age at presentation and Karnofsky performance status was 45 years and 90 respectively and male: female ratio was 20:7. Patients received adjuvant RT to a total dose of 60 Gy at 2 Gy/fraction. All patients except 5 received adjuvant TMZ to a median number of 6 cycles. Grade 2 and 3 hematological toxicity was seen in 8% and 4% of patients respectively during concurrent RT. During adjuvant chemotherapy, 13.6% had Grade 3 thrombocytopenia and 9.5% had Grade 3 neutropenia. Median OS was 16.7 months (1 year and 2 year actuarial OS was 70.8% and 32.6% respectively). Adjuvant TMZ was associated with a better survival (median survival 21.21 vs. 11.93 months; P = 0.0046) on univariate analysis and also on multivariate analysis (hazard ratio 1.82, 95% confidence interval: 1.503‑25.58; P = 0.012). CONCLUSIONS: The results of our study, largest series of patients with PGS treated with concurrent and adjuvant TMZ shows an impressive survival with acceptable toxicity. We suggest TMZ be included in the “standard of care” for this tumor.

Role of adjuvant radiation in the management of central neurocytoma: Experience from a tertiary cancer care center of India.

BACKGROUND AND OBJECTIVE: Neurocytoma (NC) is a rare benign neuronal tumor. A complete excision remains curative for most of these tumors, but atypical histology and extra‑ventricular location often necessitates adjuvant therapy. We intended to explore the clinico‑pathological features and treatment outcome in patients of NC in our institute. MATERIALS AND METHODS: Medical records were reviewed and data collected on NC over a 6‑year period (2006‑2012) from the departmental archives. Disease free survival (DFS) was analyzed by Kaplan‑Meier method. RESULTS: A total of 18 patients met the study criteria. Fourteen patients had intra‑ventricular neurocytoma (IVNC), right lateral ventricle being the most common site of origin. Gross total resection and near total resection were achieved in eight cases each whereas tumor decompression and biopsy could be done in two cases. On post‑operative histopathological examination, eight patients were found to have atypical NC while 10 patients had typical NC. All patients underwent adjuvant radiation. The median dose of post‑operative radiation was 56 Gy. All patients were alive at their final follow‑up. One patient had both clinical and radiological evidence of local relapse. In the evaluable patients (n = 18), after a median follow‑up of 35 months the DFS rate at 2 years and 3 years are 100% and 83% respectively. CONCLUSION: Use of adjuvant radiation to a total dose of 56 Gy enhances the local control and achieves superior survival in patients of NC. Use of 3D conformal planning techniques may help us to achieve better therapeutic ratio in patients with NC.

Impact of post‑operative radiation on coronary arteries in patients of early breast cancer: A pilot dosimetric study from a tertiary cancer care center from India.

BACKGROUND: The significant impact of postoperative radiotherapy (PORT) on cardiac morbidity in patients of early breast cancer (EBC) undergoing breast‑conserving surgery has been shown in different studies. The present study was conducted to assess the impact of surgery and the side of involvement on radiation dose to left anterior descending artery (LAD) and Left circumflex coronary artery (LCx). MATERIALS AND METHODS: Totally, 58 patients of EBC were randomly chosen for this dosimetric study and planned with tangential field technique without intensity modulation (IM). Heart, LAD, and LCx (n = 55) were contoured. Dose volume histograms were analyzed to determine the Dmax (maximum dose) and Dmean (mean dose) of LAD and LCx. Student’s t‑test was used for comparative analysis of the means. RESULTS: The mean Dmax of LAD for left (L) EBC was 3.17 Gray (Gy) while for right (R) EBC it was 0.86 Gy (P = 0.007; 95% C.I, 1.14–3.48). The mean Dmean of LAD for L‑EBC and R‑EBC were 1.97 Gy and 0.79 Gy, respectively (P = 0.029; 95% C.I, 0.77–1.60). The mean‑Dmax of LCx for patients with L‑EBC (2.9 Gy; range: 1.2–4.35 Gy) was statistically higher than that for R‑EBC (1.3 Gy; range: 0.7–3.2 Gy) (P = 0.045). The mean‑Dmean of LCx for L‑EBC (2.1 Gy; range: 0.6–3.6 Gy) was also significantly higher than that of L‑EBC (0.9 Gy; range: 0.7–2.1 Gy) (P = 0.03). There was no significant impact of the pattern of surgery on LAD dose, but significance was noted for LCx dose parameters (P = 0.04 and 0.08 for m‑Dmax and m‑Dmean of LCx). CONCLUSION: This pilot dosimetric study confirms the assumption that patients with left‑sided EBC are at higher risk of developing long‑term cardiac morbidity when treated with PORT due to increased dose to LAD.

Modern chemoradiation practices for malignant tumors of the trachea: An institutional experience.

Background: Malignant tumors of the trachea are rare. A multimodality treatment approach is often necessary. Outcomes of radical non-surgical approaches are sparse. Radiation combined with sequential or concurrent chemotherapy is an important treatment option. Materials and Methods: We present an analysis of outcomes using modern radiotherapy and chemotherapy for tracheal tumors. Results: Radiation dose escalation using modern techniques is of benefit for these tumors. The results with chemotherapy are encouraging. Conclusions: Radiation plays a distinct role and should be a part of treatment for these tumors. The role of chemotherapy needs to be studied further.

Role of extracorporeal irradiation in malignant bone tumors.

Aims and Objectives: Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. Materials and Methods: From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. Results: There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Conclusion: Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.

Radiation dose escalation by percutaneous interstitial brachytherapy in locally advanced non-small cell lung cancer.

Management of locally advanced non-small cell lung cancer is associated with a poor overall survival using concurrent chemoradiotherapy. Therefore, newer approaches to treatment which enable dose escalation are warranted. Interstitial brachytherapy in lung is a new emerging concept with many distinct advantages. We report here a case of locally advanced non-small cell lung cancer with residual disease after conventional treatment. The patient was successfully treated using percutaneous interstitial brachytherapy and is disease-free at 18-month follow-up.

Field-in-field technique for upper abdominal malignancies in clinical radiotherapy.

BACKGROUND: In upper abdominal malignancies (UAM), due to the presence of multiple inhomogeneous tissues, a wedge-based conformal treatment planning results in high-dose regions inside the target volume. AIM: This study was designed to explore the feasibility of using a field-in-field (FIF) technique in different UAM and its efficacy in reducing the high-dose regions. MATERIALS AND METHODS: Twelve patients of UAM (which included malignancies of the gastroesophageal junction, stomach, gall bladder, and pancreas) were selected for this study. Computed tomography (CT) scans were performed and three-dimensional conformal wedge plans were generated for all the cases. The same plan was copied with the wedges removed and a FIF plan was generated. The two plans were compared for mean, maximum, and median doses; dose received by 2% (D2) and 98% (D98) of the target volume; volume receiving> 107% (V > 107%) and < 95% (V Statistical Analysis: Statistical analysis was performed with SPSS, version 10.0. RESULTS: For all the cases, the FIF technique was better than wedge-based planning in terms of maximum dose, D2, V > 107%, and CI; there was a statistically significant reduction in monitor units. With regard to doses to critical structures, there was marginal dose reduction for the kidneys and spinal cord with FIF as compared to wedge-based planning. CONCLUSION: The FIF technique can be employed for UAM in place of wedge-based conformal treatment plans.

Normal tissue complication probability of fibrosis in radiotherapy of breast cancer: accelerated partial breast irradiation vs conventional external-beam radiotherapy.

AIMS: Radiotherapy forms an integral part of breast-conserving treatment in early-stage breast cancer. Subcutaneous fibrosis of the treated breast is an important late effect in whole-breast irradiation. The aim of this study was to compare the normal tissue complication probability (NTCP) for radiation-induced fibrosis in treated breast using accelerated partial-breast irradiation (APBI) vs conventional treatment. MATERIALS AND METHODS: Ten postoperative early-stage breast cancer patients (T1N0M0) were included in this dosimetric analysis. APBI treatment was planned using conformal radiotherapy technique and conventional treatment plans included two tangential portals. All the APBI treatment plans were made with five non-coplanar beams with 6 MV photons. The prescription dose was 38 Gy in 10 fractions for the APBI treatments and 50 Gy in 25 fractions, followed by a boost dose of 16 Gy in 8 fractions, for the conventional treatments. We used Lyman's relative-seriality model and the breast fibrosis NTCP model fitting parameters for the study. RESULTS: The equivalent uniform dose (EUD) was 30.09 Gy and 50.79 Gy in APBI and conventional treatment, respectively. The mean NTCP values for ipsilateral breast fibrosis in APBI and conventional treatment were 0.51 and 25.66%, respectively. Using the paired t-test, a statistically significant difference was seen in the breast fibrosis NTCP values for APBI vs conventional treatment (P < 0.001). CONCLUSIONS: APBI reduces the ipsilateral breast fibrosis compared to conventional whole-breast treatment in early-stage breast cancer.

Radiofrequency ablation of hepatic metastasis: results of treatment in forty patients.

AIM: To evaluate the local control of hepatic metastasis with radiofrequency ablation treatment. MATERIALS AND METHODS: We did a retrospective analysis in 40 patients treated with radiofrequency ablation for hepatic metastasis. The tumors ablated included up to two metastatic liver lesions, with primaries in breast, gastrointestinal tract, cervix, etc. Radiofrequency ablation was performed under general anesthesia in all cases, using ultrasound guidance. Radionics Cool-Tip RF System was used to deliver the treatment. RESULTS: The median age of patients treated was 49 years. There were 13 female and 27 male patients. The median tumor size ablated was 1.5 cm (0.75-4.0 cm). A total of 52 radiofrequency ablation cycles were delivered. Successful ablation was achieved in all patients with hepatic metastasis less than 3 cm in size. Pain was the most common complication seen (75%). One patients developed skin burns. At 2-year follow-up 7.5% of patients had locally recurrent disease. CONCLUSIONS: Radiofrequency ablation is a minimally invasive treatment modality. It can be useful in a select group of patients with solitary liver metastasis of less than 3 cm size.

A prospective study evaluating surgery and chemo radiation in muscle invasive bladder cancer.

AIM: The aim of our study was to compare the two standard treatment approaches in muscle invasive carcinoma of urinary bladder--radical cystectomy and chemo radiation. MATERIALS AND METHODS: Transitional cell carcinoma (TCC) of bladder of stages, T2 to T4, N0/N1/N2 and M0 were included in the study. Patients were allotted to two arms of the study. Arm A consisted of radical cystectomy. Adjuvant CMV chemotherapy was given for T3/T4 or Node positive disease only. Arm B received 2 cycles of neoadjuvant CMV chemo therapy followed by concurrent chemo radiation. RESULTS: Forty-four patients were recruited into the study. Thirty patients in the surgical arm and 13 patients in the chemo radiation arm. The actuarial two-year survival rate in surgical arm is 56% while in chemo radiation arm it is 54%. There was no statistically significant difference in disease-free survival also between the two groups. CONCLUSION: Chemo radiation yielded equivalent survival results with radical cystectomy. So it is worth giving preference to chemo radiation that will give a better quality of life for the patient.

Comparison of computed tomography and magnetic resonance based target volume in brain tumors.

PURPOSE: This study was mainly framed to study the difference in tumor volumes as seen on computed tomography (CT) and magnetic resonance (MR) and their significance in planning. MATERIALS AND METHODS: Twenty-five patients with brain tumor of different diagnoses who underwent stereotactic radiotherapy were included in this study. CT and MR imaging was done for all the patients with 2.5 mm slice thickness. The CT tumor volume and MR tumor volume were measured and compared with each other. The center of mass (CM) of the tumor volume delineated on CT and MR were computed and the shift between the two CMs was determined. RESULTS: The mean and median volume of the tumor as measured from MR scans was 19.67 cc +/- 13.73 and 16.13 cc (range: 3.25 cc-50.37 cc). Similarly, the mean and median volume of the tumor as measured from CT scans was 15.05 cc +/- 10.13 and 11.63 cc (range: 3.0 cc-36.25 cc) respectively. The mean and median CM shift between CT and MR was 5.47 mm and 5.21 mm respectively. CONCLUSION: The study demonstrates that MR is an indispensable imaging modality in radiotherapy for planning brain tumors.

Sweat gland carcinoma with lung metastases.

Sweat gland carcinoma is a rare skin tumor. The tumor has propensity to spread to lymph nodes and distant metastases has been reported. Their exact incidence in the Indian setting is not known. Aspects related to treatment are also not clearly defined. Though surgery forms the initial treatment approach, adjuvant treatment has not been properly explored. We report here a case of sweat gland carcinoma with bilateral lung metastases.

Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer: an indian experience.

BACKGROUND: Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55. The aim of t he present study was to analyze areduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage. MATERIAL AND METHODS: Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups. RESULTS: Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003), sensory neuropathy (p = 0.032) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01). CONCLUSION: Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity.

Chemotherapy related toxicity in locally advanced non-small cell lung cancer.

BACKGROUND: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB) in Indian patients using Cisplatin and Etoposide combination chemotherapy. MATERIAL AND METHODS: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0) RESULTS: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients). Nausea and vomiting were the most common non-hematological toxicity seen. Sensory neuropathy was seen in 38% of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. CONCLUSION: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

Cerebellar medulloblastoma presenting with skeletal metastasis.

Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months' duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

Imaging using Tc99m-tetrofosmin for the detection of the recurrence of brain tumour: a comparative study with Tc99m-glucoheptonate.

BACKGROUND: In the past "blood-brain barrier" agents such as Tc99m-glucoheptonate were routinely used for the diagnosis of brain tumours. Of late, agents used for studying myocardial perfusion namely, Tc99m-tetrofosmin, Thallium-201, and Tc99m-sestamibi have replaced the "blood-brain barrier agents " when imaging is undertaken for the detection of the recurrence of brain tumours. However, the incremental diagnostic information provided by Tc99m-tetrofosmin when compared with a blood brain barrier agent in the diagnosis of recurrent brain tumour has not been evaluated till date. AIMS: The study was carried out to substantiate whether Tc99m-tetrofosmin provides any incremental diagnostic information not provided by the blood brain barrier agent Tc99m-glucoheptonate. MATERIAL AND METHODS: Brain SPECT scans were performed using Tc99m-tetrofosmin and Tc99m-glucoheptonate in 126 patients of recurrent brain tumour. Bio-distribution and uptake properties of both the tracers were analysed by measuring relative uptake of both the tracers in tumour compared to background (T/B ratio), nasopharynx (T/N ratio) and scalp (T/S ratio). STATISTICAL ANALYSIS: Descriptive statistics were calculated for each variable. Pearson's correlation coefficient was applied to see agreement of the continuous variables. Paired t test was used to evaluate the difference between two means. RESULTS: Uptake properties of both the tracers were analysed in 105 patients in whom both Tc99m-tetrofosmin and Tc99m-glucoheptonate showed concentration. The remaining 21 patients in whom the tumour mass did not show Tc99m-tetrofosmin concentration were excluded from the study. Mean T/B ratio, T/N ratio and T/S ratio was 5.83 + 2.09 and 5.99 + 2.26, 0.53 + 0.21 and 0.55 + 0.22 and 1.11 + 0.60 and 1.26 + 0.52 for Tc99m-tetrofosmin and Tc99m-glucoheptonate respectively. No statistically significant difference between T/B ratio and T/N ratio of Tc99m-tetrofosmin and Tc99m-glucoheptonate was found; p values were 0.25 and 0.83 respectively. However there was significant difference (P=0.006) between the T/S ratio of Tc99m-tetrofosmin and that of Tc99m-glucoheptonate. CONCLUSION: Tc99m-tetrofosmin does not provide any incremental diagnostic information not provided by the blood brain barrier agent Tc99m-glucoheptonate.

Evaluation of single photon emission computerised tomography (SPECT) using Tc99m-tetrofosmin as a diagnostic modality for recurrent posterior fossa tumours.

BACKGROUND: Brain Single Photon Emission Computerised Tomography (SPECT) has been established as a potentially useful tool for the assessment of recurrent brain tumours. Though brain SPECT is exquisitely sensitive in detecting viable tumour tissue in the supratentorial region, its efficacy has not been evaluated till date in case of infratentorial posterior fossa tumours. AIM OF THE STUDY: To evaluate the diagnostic utility of brain SPECT in differentiating recurrence of tumour from post-radiation gliosis in the posterior fossa of the brain. SUBJECTS AND METHODS: Twenty-one patients with primary malignant posterior fossa brain tumour were evaluated by brain SPECT with Tc99m-Tetrofosmin as the tumour-seeking agent. Clinical behaviour of the tumour observed for a minimum period of one year after the SPECT study was taken as the gold standard. STATISTICAL ANALYSIS: The Chi-square test has been used to note the significance of the association between the clinical outcome and the SPECT finding. In addition, the sensitivity and specificity of brain SPECT were also calculated. RESULT: Brain SPECT in 4 patients revealed increased tracer concentration over the primary tumour bed, which was consistent with recurrent tumour. The clinical course was consistent with tumour recurrence in 13 of the 21 patients, which included 3 patients with positive SPECT study and 10 patients with negative SPECT study. Brain SPECT revealed recurrent tumour in 4 patients whereas clinical follow-up suggested recurrence in 13 patients. The clinical course was consistent with radiation necrosis in the remaining 8 patients. In 1 brain SPECT positive patient the clinical course was consistent with post-radiation gliosis. CONCLUSION: This study demonstrates that brain SPECT is not a sensitive diagnostic modality to differentiate recurrent tumour from post-radiation gliosis in the posterior fossa of the brain.

Therapeutic radiological interventional procedures in hepatocellular carcinoma.

BACKGROUND: To improve the survival rate of patients with hepatocellular carcinoma (HCC) in whom surgery is not possible, various methods have been developed employing angiographic and percutaneous techniques. We analyzed our experience with various percutaneous therapeutic interventional techniques done for HCC in our center. METHODS: Sixty-one patients with inoperable HCC (mean age 48.9 [SD 13.8] y; 47 men) were treated between January 1997 and December 2000 by transcatheter arterial chemoembolization (TACE) alone (22), TACE with percutaneous alcohol injection (PEI) (20), transcatheter arterial embolization (TAE) with steel coils and gel foam for gastrointestinal bleed (7), percutaneous radiofrequency ablation (1), percutaneous preoperative right portal vein embolization (3) and percutaneous preoperative tumor embolization to reduce blood loss at surgery (8). RESULTS: In 42 patients treated by TACE and PEI and TACE alone, tumor necrosis was scored; over 50% necrosis was seen only after six and nine months in both treatment groups. The survival rates after six and nine months and the median survival were similar in the two groups. Of 7 cases treated with TAE with steel coils and gel foam, the gastrointestinal bleeding stopped in four; in the other three, bleeding did not stop completely although less transfusion was required. In the patient treated by radiofrequency ablation, follow-up contrast-enhanced CT did not show enhancing tumor mass. We noted left lobe enlargement after percutaneous preoperative right portal vein embolization, prior to right hepatectomy. CONCLUSION: In patients with HCC not amenable to surgical intervention, a variety of percutaneous therapeutic interventional techniques may be used.