Deepinder P. Singh

Is there a favorable subset of patients with prostate cancer who develop oligometastases

OBJECTIVE To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

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.

ORAL SUCRALFATE IN ACUTE RADIATION OESOPHAGITIS

Eighty patients with carcinoma in the middle third of oesophagus and with acute radiation oesophagitis following external beam and intracavitary radiotherapy were managed by two different schedules. Group 1 (n = 40) received an antacid containing sodium alginate whereas Group 2 (n = 40) were given a 10% sucralfate suspension during 4 weeks. In Group 2, 32 patients had significant relief of symptoms within 7 days of treatment and most ulcers had healed by 12 days of treatment as seen on endoscopy. Patients in Group 1, on the other hand, showed little improvement of symptoms and had persistent ulcers even after 4 weeks of therapy. We conclude that sucralfate is useful in the management of acute radiation oesophagitis.

Local control rates with five-fraction stereotactic body radiotherapy for oligometastatic cancer to the lung

OBJECTIVE To report our institutional experience with five fractions of daily 8-12 Gy stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic cancer to the lung. METHODS Thirty-four consecutive patients with oligometastatic cancers to the lung were treated with image-guided SBRT between 2008 and 2011. Patient age ranged from 38 to 81 years. There were 17 males and 17 females. Lung metastases were from the following primary cancer types: colon cancer (n=13 patients), head and neck cancer (n=6), breast cancer (n=4), melanoma (n=4), sarcoma (n=4) and renal cell carcinoma (n=3). The median prescription dose was 50 Gy in five fractions (range, 40-60 Gy) to the isocenter, with the 80% isodose line encompassing the planning target volume (PTV) [defined as gross tumor volume (GTV) + 7-11 mm volumetric expansion]. The follow-up interval ranged from 2.4-54 months, with a median of 16.7 months. RESULTS The 1-, 2-, and 3-year patient local control (LC) rates for all patients were 93%, 88%, and 80% respectively. The 1-, 2-, and 3-year overall survival (OS) rates were 62%, 44%, and 23% respectively. The 1- and 2-year patient LC rates were 95% and 88% for tumor size 1-2 cm (n=25), and 86% for tumor size 2-3 cm (n=7). The majority (n=4) of local failures occurred within 12 months. No patient experienced local failure after 12 months except for one patient with colon cancer whose tumors progressed locally at 26 months. All five patients with local recurrences had colorectal cancer. Statistical analyses showed that age, gender, previous chemotherapy, previous surgery or radiation had no significant effect on LC rates. No patient was reported to have any symptomatic pneumonitis at any time point. CONCLUSIONS SBRT for oligometastatic disease to the lung using 8-12 Gy daily fractions over five treatments resulted in excellent 1- and 2-year LC rates. Most local failures occurred within the first 12 months, with five local failures associated with colorectal cancer. The treatment is safe using this radiation fractionation schedule with no therapy-related pneumonitis.

Second primary lung cancer after head and neck squamous cell cancer: Population-based study of risk factors†

Patients with head and neck squamous cell cancer (HNSCC) are at risk of developing second primary lung cancer (SPLC).

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.

Primary Lymphoma of the Bones of the Foot: Management of Two Cases

Non-Hodgkins lymphoma rarely presents with an osseous lesion in the foot. Two cases of primary lymphoma of the foot are reported. The patients presented with a history of pain and swelling of the foot. Radiographs revealed a lytic lesion in the calcaneus of one patient, and in the second metatarsal of the other. Open biopsy revealed high grade lymphoblastic non-Hodgkins lymphoma of the diffuse variety. The patients were treated with localized radiation therapy and have been disease free for more than a year.

Thoracic malignant solitary fibrous tumors: A population-based study of survival

INTRODUCTION This study characterizes the overall survival (OS) and cause specific survival (CSS) of patients with thoracic malignant solitary fibrous tumors. METHODS Eighty-two patients with malignant solitary fibrous tumors of the lung, pleura or mediastinum, diagnosed from 2001-2007, were retrospectively analyzed using the population-based Surveillance, Epidemiology, and End Results database. RESULTS Among 77 patients with available staging information, 42% (n=32) had localized disease, 31% (n=24) had regional disease extension (without nodal involvement) and 27% had regional-nodal (n=2) or distant (n=19) metastases. Cancer-directed surgery was performed in 85%; radiation was performed in 16%. The 1-year, 5-year and median OS were 87%, 49% and 4.6 years respectively. The 1-year, 5-year and median CSS were 89%, 61% and 5.7 years respectively. Less advanced stage and undergoing cancer-directed surgery were favorable prognostic factors. For localized, regional and distant stage the median OS was: not reached at 6.3 years, 4.4 years and 2.0 years respectively (P=0.021); the median CSS was not reached at 6.3 years, 5.0 years and 2.4 years (P=0.068). For patients undergoing versus not undergoing surgery, the median OS was 4.9 vs 0.9 years (P=0.053) and median CSS was 5.7 vs 0.9 years (P=0.011). Tumor size was not significant. CONCLUSIONS From a population-based analysis of patients with thoracic malignant solitary fibrous tumors, stage and cancer-directed surgery had the greatest impact on OS and CSS. While being amenable to surgery likely reflects more indolent disease and/or better performance status and cardiopulmonary function, the significantly favorable impact of surgery also likely reflects a therapeutic benefit.

Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: Prognostic Factors for Disease Control and Survival

Objectives: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment. Methods: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. Results: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9-27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure-free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival. Conclusions: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection.

Low-Dose Radiosurgery for Benign Intracranial Lesions

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.