Sushmita Ghoshal

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.

Dose volume histogram analysis and comparison of different radiobiological models using in-house developed software.

The purpose of this study is to compare Lyman-Kutcher-Burman (LKB) model versus Niemierko model for normal tissue complication probability (NTCP) calculation and Niemierko model versus Poisson-based model for tumor control probability (TCP) calculation in the ranking of different treatment plans for a patient undergoing radiotherapy. The standard normal tissue tolerance data were used to test the NTCP models. LKB model can reproduce the same complication probability data of normal tissue response on radiation, whereas Niemierko model cannot reproduce the same complication probability. Both Poisson-based and Niemierko models equally reproduce the same standard TCP data in testing of TCP. In case of clinical data generated from treatment planning system, NTCP calculated using LKB model was found to be different from that calculated using Niemierko model. When the fractionation effect was considered in LKB model, the calculated values of NTCPs were different but comparable with those of Niemierko model. In case of TCP calculation using these models, Poisson-based model calculated marginally higher control probability as compared to Niemierko model.

Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study.

AIMS Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting. MATERIALS AND METHODS Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared. RESULTS The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis. CONCLUSION EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied.

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.

Concomitant Boost Radiotherapy Compared with Conventional Radiotherapy in Squamous Cell Carcinoma of the Head and Neck — a Phase III Trial from a Single Institution in India

AIMS To test the efficacy of an accelerated fractionation schedule (concomitant boost) against standard conventional fractionation in squamous cell carcinomas of the head and neck region in our patient population. MATERIALS AND METHODS Patients were randomised to receive either conventional radiotherapy with 2 Gy/fraction/day, to a dose of 66 Gy in 33 fractions over 6.5 weeks or accelerated radiotherapy in the form of concomitant boost to a dose of 67.5 Gy/40 fractions over 5 weeks (phase 1: 45 Gy/25 fractions/5 weeks and phase 2: 22.5 Gy/15 fractions/3 weeks as a second daily fraction after a 6h gap). The primary and secondary end points were disease-free survival and locoregional control respectively. RESULTS The compliance was 97.2% and 96.5% in the concomitant boost and conventional arms, respectively. Patients treated with concomitant boost had a better 2-year disease-free survival (71.7% vs 52.17%, P=0.0007) and locoregional control rates (73.6% vs 54.5%, P=0.0006) than with conventional fractionation. On exploratory subgroup analysis, the oropharynx (P<0.001), T4 lesions (P=0.017), N+ disease (P<0.001) and stage IV disease (P<0.001) were statistically significant prognostic variables in favour of the concomitant boost arm. Grade 3 mucositis was seen in 35% of patients in the concomitant boost arm, whereas in the conventional arm only 19% of patients had grade 3 mucositis (P=0.01). The median radiotherapy duration in the concomitant boost arm was 36 days (range 36-53 days), whereas in the conventional arm it was 46 days (range 46-64 days). The mean gap in radiation treatment in the concomitant boost arm was 1.68 days (range 0-14 days), whereas the mean gap in the conventional arm was 1.58 days (range 0-14 days). CONCLUSIONS Concomitant boost is a therapeutically superior and logistically feasible accelerated radiotherapy regimen in advanced head and neck cancers, especially in the setting of a developing country.

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.

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.

Survival and Failure Outcomes in Primary Thyroid Lymphomas: A Single Centre Experience of Combined Modality Approach

Primary thyroid lymphoma (PTL) is a rare malignancy and represents 2%–5% of all thyroid malignancies and 1%–2.5% of all malignant lymphomas. We present our institutes experience in combined modality management of 16 successive patients of PTL treated from 2005 to 2010. The median age of the patients was 56.0 years. Five patients were males, and 11 patients were females. An enlarging thyroid mass was the most common presenting symptom. 14 patients had diffuse large B-cell lymphoma, and 2 patients had follicular lymphoma. The most common stage of presentation was stage II comprising 6 (37.5%) patients. All patients received CCT, and only 12 patients received involved field RT with a median dose of 36.0 Gy. 10 patients (62.5%) had CR, and 6 patients (27.5%) had PR. Eight patients had disease progression in subsequent followup and this included the initial 6 patients with PR. The 5-year DFS was 40.0%, and median DFS was 47 months. The 5-year OS was 41.0%, and median OS was 51 months. Most common presentation in our series was locally advanced tumors. Most of these patients require combined modality management. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity.

Breast cancer in males: A PGIMER experience

AIM Male breast cancer is a rare disease representing 1% of all breast cancers and less than 1% of all cancers in men. Because of its rarity, carcinoma breast has not been studied extensively and this prompted us to carry out this retrospective study. The aim of the study was to observe the clinical and pathological features, evaluate the prognostic factors and to co-relate the outcome in patients of male breast cancer. MATERIALS AND METHODS Thirty patients of male breast cancer treated in the department of radiotherapy from year 1996-2000 were retrospectively analyzed. RESULTS The actuarial five- year disease free survival was 40%. Three out of 30 i.e. 10% patients had loco-regional recurrence and all of them had locally advanced disease at presentation. Distant metastasis occurred in 9 patients of whom 6 patients had T3-T4 tumor and 1 patient had T1-T2 tumor. CONCLUSION Modified radical mastectomy followed by external radiation therapy is the standard treatment for male breast cancer. Hormone therapy, as an adjuvant treatment, is the first line approach in a majority of patients and chemotherapy is reserved for patients with poor prognostic factors.