Firuza D. Patel

Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: A clinical trial

PURPOSE This study is a prospective randomized clinical trial undertaken at our center to compare low dose rate versus high dose rate intracavitary brachytherapy for the treatment of carcinoma uterine cervix. METHODS AND MATERIALS From June 1986 to June 1989, 482 patients with previously untreated invasive squamous cell carcinoma of the uterine cervix were entered into the study. After an initial clinical examination and investigative work-up the patients were staged according to FIGO staging system. Depending upon the stage of the disease, the size of the local growth and the local cervical anatomy, the patients were divided into two main groups. In group I patients, the predominant treatment was by intracavitary therapy and in group II patients, the predominant therapy was by external beam radiation. In both the groups at the time of intracavity brachytherapy the patients were alternately randomized to receive either low dose rate or high dose rate brachytherapy. There were thus two hundred forty-six patients in the low dose rate group and two hundred thirty-six patients in the high dose rate group. The patients were analyzed for local control, 5 years survival and late radiation morbidity. RESULTS Stage for stage the local control rates in the low dose rate group and high dose rate group were similar. The overall local control achieved in the low dose rate group was 79.7% as compared to 75.8% in the high dose rate group. The 5 years survival figures in the low dose rate and high dose rate group were also comparable. In Stage I, it was 73% for low dose rate patients and 78% for high dose rate patients, for Stage II it was 62% and 64% respectively and for Stage III patients it was 50% and 43%. The only statistically significant difference was found in the incidence of overall rectal complications which was 19.9% for the low dose rate group as compared to only 6.4% for the high dose rate group. However, the more severe grade 3-4 complications were not significantly different between the two groups (2.4% vs. 0.4%, respectively). The bladder morbidity in both the groups was similar. CONCLUSION Thus high dose rate intracavitary brachytherapy is an equally good alternative to conventional low dose rate brachytherapy in the treatment of carcinoma of the uterine cervix.

Radiation therapy of esophageal cancer: Role of high dose rate brachytherapy

Fifty untreated cases of squamous cell carcinoma arising from the middle one-third of the esophagus, with no apparent extraesophageal spread on a computed tomography (CT) scan and with a Karnofsky performance status of over 70, were treated by external beam irradiation to a dose of 3500 cGy/15 fractions/3 weeks. Twenty-five patients (Group A) received treatment with further external beam irradiation to a dose of 2000 cGy/10 fractions/2 weeks. Another group of 25 patients (Group B) received treatment with high dose rate intracavitary irradiation to a dose of 1200 cGy delivered in two sessions of 600 cGy each a week apart. All patients were assessed symptomatically, endoscopically, and radiologically every 3 months. There was marked difference at the end of 1 year in relief of dysphagia (37.5% in Group A vs. 70.6% in Group B), local control (25% in group A vs. 70.6% in group B) although the results were statistically insignificant (p greater than 0.05) and actuarial survival (44% in group A vs. 78% in group B) which was, however, significant statistically (z = 2.83). The cumulative radiation effect (CRE) by external beam irradiation was 1729 reu and by external beam and intracavitary irradiation 1741 reu, but the biological dose effect was better with external beam and intracavitary irradiation. Eight percent of patients treated by external beam and intracavitary irradiation had strictures in contrast to 4% treated by external beam irradiation alone. Moderate doses of external beam and intracavitary irradiation can give a better local response than external beam irradiation alone for the same biological dose in the treatment of esophageal carcinoma.

Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

The aim was to determine whether promoter methylation of BRCA1, MGMT, MLH1, RASSF1A, and p16 genes could predict response to platinum-based chemotherapy. Thirty-five subjects with epithelial ovarian cancer (EOC) treated by platinum-based chemotherapy were recruited. Methylation-specific polymerase chain reaction was carried out and the methylation index (MI) was also derived. Response to platinum-based chemotherapy was documented clinically, radiologically, and by serial CA125 levels. Methylated BRCA1 (p =. 037) and a higher MI (p =. 045) were associated with primary chemosensitivity. A better outcome was predicted by a higher MI (p =. 032). In EOC, BRCA1 gene promoter methylation is useful in the prediction of response to chemotherapy.

Palliative care in India: current progress and future needs.

Despite its limited coverage, palliative care has been present in India for about 20 years. Obstacles in the growth of palliative care in India are too many and not only include factors like population density, poverty, geographical diversity, restrictive policies regarding opioid prescription, workforce development at base level, but also limited national palliative care policy and lack of institutional interest in palliative care. Nonetheless we have reasons to be proud in that we have overcome several hurdles and last two decades have seen palpable changes in the mindset of health care providers and policy makers with respect to need of palliative care in India. Systematic and continuous education for medical staff is mandatory, and a major break-through for achieving this purpose would be to increase the number of courses and faculties in palliative medicine at most universities.

Side-effects of local hyperthermia: Results of a prospectively randomized clinical study

In 1986, 25 patients with stage II and III carcinoma of the cervix were treated by a combination of radiation and local hyperthermia using an endotract intravaginal applicator. Another 25 patients were treated with radiation alone. Both groups were followed up for a minimum period of 18 months. The acute and long-term toxicity of local hyperthermia was closely monitored. Our study shows that whereas local hyperthermia adds significantly to the local control achieved with radiation alone, it is not in any way associated with any significant short- or long-term toxicity, and does not enhance the radiation reactions.

Dose rate correction in medium dose rate brachytherapy for carcinoma cervix

PURPOSE To establish the magnitude of brachytherapy dose reduction required for stage IIB and III carcinoma cervix patients treated by external radiation and medium dose rate (MDR) brachytherapy at a dose rate of 220+/-10 cGy/h at point A. MATERIALS AND METHODS In study-I, at the time of MDR brachytherapy application at a dose rate of 220+/-10 cGy/h at point A, patients received either 3060 cGy, a 12.5% dose reduction (MDR-12.5), or 2450 cGy, a 30% dose reduction (MDR-30), to point A and they were compared to a group of previously treated LDR patients who received 3500 cGy to point A at a dose rate of 55-65 cGy/h. Study-II was a prospective randomized trial and patients received either 2450 cGy, a 30% dose reduction (MDR-II (30)) or 2800 cGy, a 20% dose reduction (MDR-II (20)), at point A. Patients were evaluated for local control of disease and morbidity. RESULTS In study-I the 5-year actuarial local control rate in the MDR-30 and MDR-12.5 groups was 71.7+/-10% and 70.5+/-10%, respectively, compared to 63.4+/-10% in the LDR group. However, the actuarial morbidity (all grades) in the MDR-12.5 group was 58.5+/-14% as against 34.9+/-9% in the LDR group (P < 0.05). Similarly, the grade III and IV morbidity also in the MDR-12.5 group was 12.5+/-9% as against 5.3+/-5% in the LDR group (P < 0.05). No statistically significant difference in morbidity was seen between the MDR-30 and LDR groups. In study-II the 3-year actuarial local control rate in the MDR-II (30) and MDR-II (20) groups was 66.6+/-10% and 74.8+/-9%, respectively. There was a significant correlation between the rectal BED received and the percentage of patients developing rectal morbidity. Only 10% of patients receiving a rectal BED of (100 < 120) Gy3 developed complication as against 62.5% of those receiving a rectal BED of (140 < 160) Gy3 (chi2 = 46.43; P < 0.001). CONCLUSION We suggest that at a dose rate of 220+/-10 cGy/h at point A the brachytherapy dose reduction factor should be around 30%, as suggested by radiobiological data, to keep the morbidity as low as possible without compromising the local control rates.

Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

PURPOSE To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. METHODS AND MATERIALS Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. RESULTS Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. CONCLUSION The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

CT or MRI for Image-based Brachytherapy in Cervical Cancer

OBJECTIVE To compare volumes and doses of tumour and organs at risk with computed tomography vs. magnetic resonance imaging in cervical cancer brachytherapy. METHODS Seventeen previously untreated patients with cervical cancer suitable for radical treatment were included. All patients underwent brachytherapy using a magnetic resonance imaging-compatible applicator followed by both computed tomography and magnetic resonance imaging. The tumour and organs at risk (bladder, rectum, sigmoid and intestines) were contoured on computed tomography using only clinical findings and on magnetic resonance imaging using GEC-ESTRO guidelines. The volume and doses for tumour and organs at risk were evaluated using two-sided t-test. RESULTS When magnetic resonance imaging information is not included in contouring on computed tomography images, there is significant underestimation of tumour height and overestimation of the width (P< 0.05). However, there was no significant difference in V(100), D(90) and D(100) for high- and intermediate-risk clinical target volume in computed tomography and magnetic resonance imaging. The volumes and doses to 0.1, 1 and 2 cc for organs at risk were also similar. CONCLUSIONS Magnetic resonance imaging remains the gold standard for tumour delineation, but computed tomography with clinical information can give comparable results, which need to be studied further. Computed tomography-based contouring can be used comfortably for delineation of organs at risk.

Primary gliosarcoma – clinical experience from a regional cancer centre in north India

Aims. We intended to assess the clinicopathological features and treatment outcome in patients of primary gliosarcoma, a rare malignant brain tumour. Materials and methods. Medical records were reviewed and data collected on primary gliosarcoma over an 8-year period (2002–2009) from the departmental archives. Overall survival (OS) was analysed by Kaplan–Meier method. Results. Seventeen patients met the study criterion (male:female = 9:8). Median age and performance status at presentation were 50 years and Karnofsky performance scale (KPS) 70, respectively. Symptoms of raised intracranial tension (in 100%) and motor impairment (in 64.7%) were commonly observed. Tumour location was frontal in four patients, temporal in three, parietal in three, thalamic in one, multilobed in five and multicentric in one. All patients underwent maximal safe surgery (total excision-10, near-total excision-2, subtotal excision and decompression-5). On histopathology, all tumours showed biphasic pattern, glial component positive for glial fibrillary acidic protein (GFAP) and mesenchymal component positive for vimentin and reticulin. Atypia, mitoses, necrosis and endothelial proliferation were identified in the glial component. Post-operative radiotherapy (median dose – 60 Gy/30#/6 weeks) was used in 15 patients (88.2%). Concurrent and adjuvant chemotherapy with temozolomide (TMZ) were used in two patients depending upon affordability. After the completion of treatment, 35.3% patients were asymptomatic, 23.5% had symptomatic improvement, while 41.2% deteriorated. Salvage therapy for local recurrence was used in three patients (temporal lobectomy-1; total excision-1; TMZ+ bevacizumab-1). At last follow-up (FU), eight patients were alive, seven patients dead and two patients lost to FU with symptom. Median overall survival in the evaluable patients (N = 15) was noted to be 8.27 months (6 month survival 60.76%). Conclusions. Primary gliosarcoma, a variant of glioblastoma poses clinical challenge because of rarity, poor prognosis and limited experience. In our centre, principle of therapy is akin to that of glioblastoma – surgery followed by radiation along with concurrent and adjuvant TMZ. However, chemotherapy is often cost-prohibitive in our setting as mirrored by limited use (17.6%). Median survival of only 8.27 months in our series is in concert with the existing survival result of primary gliosarcoma in world literature (6.25–11.5 months).

Quad shot: A short but effective schedule for palliative radiation for head and neck carcinoma

Background: To evaluate a 2-day course of palliative radiation in patients diagnosed to have inoperable or metastatic head and neck carcinoma. Aim: To evaluate the symptom relief and quality of life in these patients after this short course of radiation. Settings and Design: A pilot study was conducted in a tertiary care institute in India. Materials and Methods: Fifteen patients with stage IV B/C disease, KPS 50-70, were inducted after informed consent. External radiation was given in 2 days, two fractions per day, 6 h apart to a total dose of 14 Gy. Washington University quality of life questionnaire (QOL) was used for assessing QOL before and after radiation. Patients who had more than 50% regression of disease received a second course of similar radiation. All patients were followed up for a mean duration of 6 months. Statistical Analysis: The Wilcoxon signed rank test was used to evaluate the difference between the QOL scores before and after treatment. Results and Conclusions: Out of these 15 patients, majority (13) were males and the mean age of the patients was 62 years. After the first course, all patients had good symptom relief, improvement in the QOL, and 13 out of 15 had more than 50% objective response. The short duration of the treatment was favored by the outstation patients and their attendants. It may be concluded that this short course of radiation is an effective tool for palliative radiation and merits a larger randomized trial.