Biomedical subjects

Anurag K Singh

Publications and source records attributed to Anurag K Singh.

14 recordsLinked to original sources

PubMed2006

Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant.

PURPOSE: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. METHODS AND MATERIALS: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n=85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n=35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n=26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. RESULTS: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO)<100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p=0.042). CONCLUSION: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

Adult↗

PubMed2006

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: implications for radiation dose escalation in carcinoma of the pancreas.

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.

Dose-Response Relationship, Radiation↗

PubMed2006

Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided high dose rate brachytherapy boost.

PURPOSE: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. RESULTS: Median follow-up was 24 months (range 18-36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. CONCLUSION: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.

Aged↗

PubMed2006

Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: a pilot study.

PURPOSE: Our goal was to test the ability of intrarectal amifostine to limit symptoms of radiation proctitis. METHODS AND MATERIALS: The first 18 patients received 1 g of intrarectal amifostine suspension placed 30-45 min before each radiation treatment. The following 12 patients received 2 g of amifostine. Total dose prescribed ranged from 66 to 76 Gy. All patients were treated with three-dimensional conformal radiation therapy. The suspension remained intrarectal during treatment and was expelled after treatment. For gastrointestinal symptoms, during treatment and follow-up, all patients had a Radiation Therapy Oncology Group (RTOG) grade recorded. RESULTS: Median follow-up was 18 months (range, 6-24 months). With 2 g vs. 1 g amifostine, there was a nearly significant decrease in RTOG Grade 2 acute rectal toxicity. Seven weeks after the start of radiation therapy, the incidence of Grade 2 toxicity was 33% in the 1-g group (6/18) compared with 0% (0/12) in the 2-g group (p=0.06). No Grade 3 toxicity or greater occurred in this study. CONCLUSION: This trial suggests greater rectal radioprotection from acute effects with 2 g vs. 1 g amifostine suspension. Further studies should be conducted in populations at higher risk for developing symptomatic acute and late proctitis.

Administration, Rectal↗

PubMed2006

Cisplatin chemotherapy (without erythropoietin) and risk of life-threatening thromboembolic events in carcinoma of the uterine cervix: the tip of the iceberg? A review of the literature.

BACKGROUND: The risk of severe cardiovascular toxicity, specifically thromboembolic events (TE), in patients with cervical cancer receiving concurrent irradiation and cisplatin chemotherapy is reported to be less than 1% in several large prospective trials. However, the anecdotal risk appears to be far higher. RESULTS AND DISCUSSION: A review of several prospective trials demonstrates no treatment related grade 4 cardiovascular toxicities and only two grade 5 toxicities in 1424 (0.1%) collective patients. A recent publication and our own unpublished experience finds 6 of 128 (4.7%) patients developed grade 4 to 5 cardiovascular (thrombosis/embolism) toxicity. The difference in incidence of severe or life threatening cardiovascular toxicity of 0.1 versus 4.7% is highly statistically significant (p < 0.00001.) CONCLUSION: This dramatic difference in incidence of cardiovascular toxicity raises the possibility that cardiovascular toxicities were inadequately reported on the listed prospective trials. For those patients enrolled in prospective trials, we suggest that thromboses should be diligently documented and reported. Only after the true incidence of thromboses is established can we implement appropriate levels of early screening and intervention that may prevent life threatening complications.

Antineoplastic Agents↗

PubMed2006

Monitoring the effect of mild hyperthermia on tumour hypoxia by Cu-ATSM PET scanning.

PURPOSE: Mild hyperthermia can improve tumour oxygenation and enhance radiosensitivity. Imaging the hypoxic fraction of a tumour can guide hyperthermia treatment planning and facilitate treatment optimization. 64Cu-ATSM (Copper-diacetyl-bis(N4-methylthiosemicarbazone)) is a positron emitting compound that has been demonstrated to have rapid uptake and selective retention in hypoxic cells and has been used for imaging human and animal tumours. The purpose of the present report is to establish methodology that will allow one to use Cu-ATSM PET scanning to detect the impact of hyperthermia on tumour physiology in as little time as possible. MATERIALS AND METHODS: EMT6 tumours (mouse mammary carcinoma) were implanted into the subcutaneous tissue of both thighs of 10 BALB/c mice (one heated, one control tumour per animal). The target thermal dose was 41.5 degrees C x 45 min. Without interrupting heating, 64Cu-ATSM (mean activity 1.8 mCi) was then injected and serial PET scans were obtained. In a sub-group of four animals, a low administered activity (approximately 0.3 mCi) 64Cu-ATSM scan was also conducted before heating to permit a direct comparison of the effects of hyperthermia on the same tumours. In another sub-group of five animals, a low activity (approximately 0.3 mCi) 64Cu-PTSM (pyruvaldehyde-bis(N*-methylthiosemicarbazone)) scan was conducted before heating, to confirm a posited correlation between perfusion and early 64Cu-ATSM uptake. RESULTS: This study corrected for perfusion differences by dividing tumour uptake by the average early (first minute) uptake ('self-normalized uptake'). The 10 heated tumours showed a significantly (p = 0.007) lower self-normalized uptake than control tumours by 2 min. For the four mice with low activity Cu-ATSM scans performed before hyperthermia, the tumours to be heated demonstrated self-normalized uptake consistent with the unheated control tumours and which departed significantly (p < or = 0.02) from their post-hyperthermia scans by 5 min. Comparisons between scans and needle electrode surveys were performed in an additional four animals with eight tumours. For technical reasons electrode surveys were done after the end of hyperthermia-and, therefore, these animals also had comparison scans taken after hyperthermia. Reduced self-normalized uptake on scans was associated with increased pO2 on electrode surveys. These data also suggested a substantial degradation of the effect on tumour hypoxia by approximately 15-45 min after the end of mild hyperthermia. CONCLUSION: Short imaging times of approximately 5 min with modest (approximately 4-10) numbers of mice can discriminate the effects of mild hyperthermia on tumour physiology. The long-term objective is to use this tool to identify as short and mild a hyperthermia session as possible.

Animals↗

PubMed2006

Alkaline phosphatase level increase with initiation of hormone therapy for prostate cancer portends poor prognosis with rapid progression to bone metastases: a case report and review of the literature.

A 73-year-old man with localized prostate cancer was treated with androgen deprivation and radiation therapy. Staging evaluation showed no evidence of metastatic disease. After initiation of androgen deprivation therapy, the patient developed a marked increase in serum alkaline phosphatase (ALP). Despite continuation of hormonal ablation and completion of radiation therapy, ALP and prostate-specific antigen levels continued to increase. Bone metastases were documented 6 months after diagnosis. In this report, we explore the role of serum ALP as an indicator for patients who develop early metastases and thus might benefit from early initiation of aggressive secondary treatments such as chemotherapy.

Aged↗

PubMed2005

Results of the 2003 Association of Residents in Radiation Oncology (ARRO) surveys of residents and chief residents in the United States.

PURPOSE: To document demographic characteristics of current residents, career motivations and aspirations, and training program policies and resources. METHODS: In 2003, the Association of Residents in Radiation Oncology (ARRO) conducted two nationwide surveys: one of all U.S. radiation oncology residents and one of chief residents. RESULTS: The Chief Residents' Survey was completed by representatives from all 77 programs (response rate, 100%). The Residents' Survey was returned by 229 respondents (response rate, 44%). In each, 32% of respondents were female. The most popular career after residency was private practice (46%), followed by permanent academic practice (28%). Changes that would entice those choosing private practice to consider an academic career included more research experience as a resident (76%), higher likelihood of tenure (69%), lesser time commitment (66%), and higher salary (54%). Although the majority of respondents were satisfied with educational experience overall, a number of programs were reported to provide fewer resources than required. CONCLUSIONS: Median program resources and numbers of outliers are documented to allow residents and program directors to assess the relative adequacy of experience in their own programs. Policy-making bodies and individual programs should consider these results when developing interventions to improve educational experiences of residents and to increase retention of radiation oncologists in academic practice.

Adult↗

PubMed2005

Cervix carcinoma, concurrent chemoradiotherapy, and salvage of isolated paraaortic lymph node recurrence.

PURPOSE: To determine the effect of concurrent chemoradiotherapy on the outcome of invasive cervical carcinoma patients with disease recurrence isolated to the paraaortic lymph nodes. METHODS AND MATERIALS: Between 1987 and 2003, 816 cervical carcinoma patients received radiotherapy at Mallinckrodt Institute of Radiology. Of these 816 patients, 14 had clinically or radiographically detected isolated paraaortic lymph node metastases. Before 1998, imaging was done if warranted by the presence of one or more classic findings, including lower extremity edema, sciatic pain, and hydronephrosis. After 1998, radiographic imaging was a routine part of follow-up for all patients. The median age at recurrence was 42.5 years (range, 32-54 years). Follow-up for all living patients was current at last follow-up. Full-dose radiotherapy equaled at least 45 Gy. RESULTS: All 7 patients with a classic finding of recurrence, none of whom had been treated to at least 45 Gy and concurrent chemotherapy, were dead of disease within 1.5 years. The 7 patients without a classic finding of recurrence, all of whom had been treated with salvage full-dose concurrent chemoradiotherapy, had a 5-year overall survival rate of 100% (p <0.01). CONCLUSION: Salvage concurrent full-dose chemoradiotherapy afforded excellent survival of patients who did not have classic findings but had disease recurrence exclusively in the paraaortic lymph nodes. The effectiveness of salvage concurrent full-dose chemoradiotherapy in patients with symptomatic disease recurrence remains unclear. However, chemotherapy or radiotherapy alone produced dismal survival in patients with classic findings of recurrence.

Adult↗

PubMed2005

Quantitation of the reconstruction quality of a four-dimensional computed tomography process for lung cancer patients.

We have developed a four-dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (1.5 mm slices) operated in ciné mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (0.5 s rotation, 0.25 s between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry-sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal-object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air-containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content (V). The relationship between the air content and spirometer-measured tidal volume (v) was found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume-sorted 4D CT. Inspection of the CT-scan air content as a function of tidal volume showed excellent correlations (typically r>0.99) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was 1.08 +/- 0.06, indicating the high quality of spirometry-based image sorting. The residual of a first-order fit between v and V was used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of 5.1% +/- 1.9%. This quantitative analysis highlights the value of using spirometry as the metric in sorting CT scans. The 4D reconstruction provides the CT data required to measure the three-dimensional trajectory of tumor and lung tissue during free breathing.

Air↗

PubMed2004

Lymph node control in cervical cancer.

PURPOSE: The aim was to evaluate pretreatment lymph node size, irradiation dose, and failure patterns. METHODS: Pretreatment PET and CT were performed in 208 patients. Lymph nodes were scored as either positive or negative by PET and lymph node size was measured by CT. Lymph node irradiation dose and sites of failure were recorded. RESULTS: The mean pelvic lymph node doses were: PET negative nodes, < or =1 cm, 66.8 Gy, and 0/76 failures; PET positive nodes, < or =1 cm, 66.8 Gy, and 3/89 failures; 1.1-< or =2 cm, 66.9 Gy, and 0/21 failures; 2.1-< or =3 cm, 69.4 Gy, and 2/15 failures; and 3.1 to < or =4 cm, 74.1 Gy, and 0/5 failures. The mean paraaortic lymph node dose was 43.3 Gy and there were no paraaortic failures for 24 patients with PET positive < or =1 cm nodes, 0/5 failures for 1.1 to < or =2 cm, and 0/4 failures for 2.1 to < or =3 cm. The most common site of failure was distant metastases. CONCLUSIONS: The irradiation doses given in this study were adequate to control most lymph node metastases. Positive lymph nodes of any size at diagnosis were the most significant predictor for developing distant metastases.

Adult↗

PubMed2003

The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer.

PURPOSE: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences. PATIENTS AND METHODS: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS). RESULTS: Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2. CONCLUSIONS: The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.

Academic Medical Centers↗

PubMed2003

FDG-PET lymph node staging and survival of patients with FIGO stage IIIb cervical carcinoma.

PURPOSE: To evaluate the outcome of patients with International Federation of Gynecology and Obstetrics (FIGO) clinical Stage IIIb cervical carcinoma as a function of site of initial regional lymph node metastasis as detected by 2[18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET). METHODS AND MATERIALS: Forty-seven patients with FIGO Stage IIIb cervical cancer were evaluated before therapy with whole-body FDG-PET. Most patients were treated with external beam irradiation, intracavitary brachytherapy, and weekly cisplatin for six cycles. Overall and cause-specific survival rates were calculated by the Kaplan-Meier method. RESULTS: The pretreatment whole-body FDG-PET demonstrated that all patients had FDG uptake in the cervix. Of 47 patients, 13 (28%) had no evidence of lymph node metastasis, 20 (43%) had metastasis to pelvic lymph nodes only, 7 (15%) had pelvic and para-aortic lymph node metastases, and 7 (15%) had metastases to pelvic, para-aortic, and supraclavicular lymph nodes. The 3-year estimate of cause-specific survival was 73% for those with no lymph node metastasis, 58% for those with only pelvic lymph node metastasis, 29% for those with pelvic and para-aortic lymph node metastases, and 0% for those with pelvic, para-aortic, and supraclavicular lymph node metastasis (p = 0.0005). CONCLUSION: The cause-specific survival for patients with FIGO Stage IIIb carcinoma is highly dependent on the extent of lymph node metastasis as demonstrated by whole-body FDG-PET.

Adult↗

PubMed2003

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. RESULTS: Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Acute Disease↗