Preoperative chemoradiation for advanced vulvar cancer reduces the tumor size and decreases morbi... more Preoperative chemoradiation for advanced vulvar cancer reduces the tumor size and decreases morbidity from operative resection. A woman with locally advanced vulvar cancer had no evidence of metastatic disease at presentation. She displayed complete resolution of her vulvar and groin disease but developed early metastatic spread to the lungs and bone. Despite excellent local control, patients with locally advanced vulvar cancer are at risk for early metastatic spread. The effect of delayed surgical intervention, ifany, is unknown.
Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage ac... more Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage achievable by single-channel applicator (SC) and comparable to Syed plan simulation. Twenty-eight plans were evaluated from four patients with primary or recurrent gynecologic cancer in the vagina. Each received whole pelvis radiation, followed by three weekly treatments using HDR brachytherapy with a 13-channel MC. Upper vagina was treated to 5 mm depth to 1500 cGy/3 fractions with a simultaneous integrated boost totaling 2100 cGy/3 fractions to tumor. Modeling of SC and Syed plans was performed using MC scans for each patient. Dosimetry for MC and SC plans was evaluated for PTV700 cGy coverage, maximum dose to 2 cm(3) to bladder, rectum, as well as mucosal surface points. Dosimetry for Syed plans was calculated for PTV700 cGy coverage. Patients were followed for treatment response and toxicity. Dosimetric analysis between MC and SC plans demonstrated increased tumor coverage (PTV700 cGy), with decreased rectal, bladder, and contralateral vaginal mucosa dose in favor of MC. These differences were significant (p < 0.05). Comparison of MC and Syed plans demonstrated increased tumor coverage in favor of Syed plans which were not significant (p = 0.71). Patients treated with MC had no cancer recurrence or ≥grade 3 toxicity. Use of MC was efficacious and safe, providing superior coverage of tumor volumes ≤1 cm depth compared to SC and comparable to Syed implant. MC avoids excess dose to surrounding organs compared to SC, and potentially less morbidity than Syed implants. For tumors extending ≤1 cm depth, use of MC represents an alternative to an interstitial implant.
A subgroup of prostate cancer patients who have experienced biochemical relapse after radical ret... more A subgroup of prostate cancer patients who have experienced biochemical relapse after radical retropubic prostatectomy (RRP) can benefit from radiation therapy to the prostate fossa. These patients demonstrate biochemical relapse secondary to local failure in the absence of distant failure. In order to define this subgroup, we investigated the impact of pathological and biochemical variables and pre-radiation therapy biopsy of the prostate fossa on biochemical disease-free survival (bNED) and initial prostate-specific antigen response. Sixty-two patients with localized prostate cancer who had biochemical relapse after RRP were treated with post-RRP radiation therapy localized to the prostate fossa (median dose, 6120 cGy) and were subsequently followed up for a median time of 47 months. Cox regression analyses and Kaplan-Meier estimates for bNED were used to identify prognostic variables. The Fisher's exact test was used to test the interaction of initial prostate-specific antige...
In February 1999, the National Cancer Institute (NCI) issued a clinical alert based on five rando... more In February 1999, the National Cancer Institute (NCI) issued a clinical alert based on five randomized trials that reported better overall survival (OS) with concurrent chemoradiotherapy (CCRT) than with surgery or radiation alone for locoregional cervical cancer. This study analyzes data from the surveillance epidemiology and end results (SEER) program to evaluate the improvement in survival in the era of CCRT. The SEER database was queried for FIGO stages IB2-IVA cervical cancer patients treated with radiotherapy between 1995 and 2002. Patients diagnosed between 1999 and 2002 (CCRT era) were assumed to have received CCRT more frequently than patients diagnosed between 1995 and 1998 (RT era). Cases were stratified by period of diagnosis, age, and SEER region. OS and cause specific survival (CSS) were compared between the two time periods with chi-square log-rank tests. Multivariable Cox models were also used to compare OS and CSS between the two time periods, with adjustment for st...
Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients ... more Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients present with extensive stage of the disease. To reduce the high risk of brain metastases, prophylactic cranial irradiation has been shown to be very effective. Prophylactic cranial irradiation should now routinely be used for all patients who have responded to chemotherapy. Thoracic radiotherapy is often reserved for palliation. However, the high incidence of residual disease after chemotherapy and the reported beneficial effect of radiotherapy in a single study has led to two clinical trials which will soon open and address the question whether thoracic radiotherapy also has a role in responding patients with extensive stage small cell lung cancer.
A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediate... more A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in non-targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4 monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human monoclonal anti-CTLA-4 antibody) induced immune-mediated abscopal effects in poorly immunogenic pre-clinical tumor models and metastatic melanoma patients. However, no such reports exist for patients with metastatic lung adenocarcinoma. We report the first abscopal response in a treatment-refractory lung cancer patient treated with radiotherapy and ipilimumab. A post-treatment increase in tumor-infiltrating cytotoxic lymphocytes, tumor regression, and normalization of tumor markers was observed. One year after treatment with concurrent radiotherapy and ipilimumab the patient is without evidence of disease.
Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosi... more Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosis and resulting in a block of the cell cycle at G2 and M. The drug is isolated from the yew, Taxus sp. L., and is currently being evaluated in a series of Phase II and Phase III clinical trials. Taxol blocks cells in the most radiosensitive phases of the cell cycle and thus could act as a cell cycle-specific radiosensitizer. We report the results of combined taxol-radiation exposures in the human Grade III astrocytoma cell line, G18. Taxol is a potent inhibitor of G18 cell division; a concentration of 10 nM is cytostatic for a cell population observed for at least two doubling times. Cell survival curves for G18 cells showed a significant concentration-dependent interaction between taxol and radiation. Treatment of G18 cells with a fixed taxol concentration and radiation dose showed the interaction to be dependent on the duration of taxol exposure and consequently the fraction of cells i...
To evaluate the prognostic significance of prostate-specific antigen density (PSAD) in clinically... more To evaluate the prognostic significance of prostate-specific antigen density (PSAD) in clinically localized prostate cancer and determine whether this index is independent of or superior to prostate-specific antigen (PSA) in predicting outcome of patients treated with external beam radiotherapy. Between January 1989 and December 1993, 175 evaluable patients with clinically localized prostate cancer received definitive radiotherapy using computed tomography (CT)-guided conformal techniques. PSAD was defined as the ratio of the pretreatment serum PSA to the prostate volume measured from CT treatment planning scans by one investigator. All PSA values were determined using the Hybritech assay. Biochemical failure was defined as two consecutive elevations in PSA separated by at least 3 months and a final PSA value greater than 1 ng/mL. Multivariate analysis including PSA and Gleason score revealed both to be statistically significant predictors of biochemical disease-free survival (P = 0.048 and P < 0.001, respectively). PSAD did not achieve significance on regression analysis. A direct multivariate analysis including PSA and PSAD required dichotomization in order to reduce high correlation. This analysis demonstrated a relative risk (RR) for failure of 1.27 (NS) for high PSA versus low PSA compared with a RR of 1.20 (NS) for high PSAD versus low PSAD. A regression model containing all three variables indicated only the Gleason score as significant in predicting biochemical failure. These data do not suggest that PSAD is either an independent prognostic factor or a stronger discriminant of outcome than PSA in patients with clinically localized prostate cancer treated with definitive external beam radiotherapy. Larger patient numbers with longer follow-up data, use of a clinical end point, or an analysis restricted to the appropriate subgroup may demonstrate the utility of PSAD in the future.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, Jan 27, 2008
Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often... more Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast-cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study...
2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263), 2001
Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate... more Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy of prostate cancer. Yet no imaging modality, including B-mode images, reliably shows cancerous lesions of the prostate. Tissue-typing imaging based on spectrum analysis of ultrasonic radio-frequency (RF) echo signals may be able to overcome the limitations of conventional imaging modalities for visualizing
Medical Imaging 2004: Ultrasonic Imaging and Signal Processing, 2004
Our research is intended to develop ultrasonic methods for characterizing cancerous prostate tiss... more Our research is intended to develop ultrasonic methods for characterizing cancerous prostate tissue and thereby to improve the effectiveness of biopsy guidance, therapy targeting, and treatment monitoring. We acquired radio-frequency (RF) echo-signal data and clinical variables, e.g., PSA, during biopsy examinations. We computed spectra of the RF signals in each biopsied region, and trained neural network classifers with over 3,000
Breath testing could provide a rational tool for radiation biodosimetry because radiation causes ... more Breath testing could provide a rational tool for radiation biodosimetry because radiation causes distinct stress-producing molecular damage, notably an increased production of reactive oxygen species. The resulting oxidative stress accelerates lipid peroxidation of polyunsaturated fatty acids, liberating alkanes and alkane metabolites that are excreted in the breath as volatile organic compounds (VOCs). Breath tests were performed before and after radiation therapy over five days in 31 subjects receiving daily fractionated doses: 180-400 cGy d(-1) standard radiotherapy (n = 26), or 700-1200 cGy d(-1) high-dose stereotactic body radiotherapy (n = 5). Breath VOCs were assayed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Multiple Monte Carlo simulations identified approximately 50 VOCs as greater-than-chance biomarkers of radiation on all five days of the study. A consistent subset of 15 VOCs was observed at all time points. A radiation respo...
Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate... more Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning radiotherapy (i.e., brachytherapy and external-beam radiation) of prostate cancer (CaP). Yet B-mode images essentially do not allow visualization of cancerous lesions of the prostate. Ultrasonic tissue-typing imaging based on spectrum analysis of radio-frequency (RF) echo signals has shown promise for overcoming the limitations
Preoperative chemoradiation for advanced vulvar cancer reduces the tumor size and decreases morbi... more Preoperative chemoradiation for advanced vulvar cancer reduces the tumor size and decreases morbidity from operative resection. A woman with locally advanced vulvar cancer had no evidence of metastatic disease at presentation. She displayed complete resolution of her vulvar and groin disease but developed early metastatic spread to the lungs and bone. Despite excellent local control, patients with locally advanced vulvar cancer are at risk for early metastatic spread. The effect of delayed surgical intervention, ifany, is unknown.
Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage ac... more Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage achievable by single-channel applicator (SC) and comparable to Syed plan simulation. Twenty-eight plans were evaluated from four patients with primary or recurrent gynecologic cancer in the vagina. Each received whole pelvis radiation, followed by three weekly treatments using HDR brachytherapy with a 13-channel MC. Upper vagina was treated to 5 mm depth to 1500 cGy/3 fractions with a simultaneous integrated boost totaling 2100 cGy/3 fractions to tumor. Modeling of SC and Syed plans was performed using MC scans for each patient. Dosimetry for MC and SC plans was evaluated for PTV700 cGy coverage, maximum dose to 2 cm(3) to bladder, rectum, as well as mucosal surface points. Dosimetry for Syed plans was calculated for PTV700 cGy coverage. Patients were followed for treatment response and toxicity. Dosimetric analysis between MC and SC plans demonstrated increased tumor coverage (PTV700 cGy), with decreased rectal, bladder, and contralateral vaginal mucosa dose in favor of MC. These differences were significant (p < 0.05). Comparison of MC and Syed plans demonstrated increased tumor coverage in favor of Syed plans which were not significant (p = 0.71). Patients treated with MC had no cancer recurrence or ≥grade 3 toxicity. Use of MC was efficacious and safe, providing superior coverage of tumor volumes ≤1 cm depth compared to SC and comparable to Syed implant. MC avoids excess dose to surrounding organs compared to SC, and potentially less morbidity than Syed implants. For tumors extending ≤1 cm depth, use of MC represents an alternative to an interstitial implant.
A subgroup of prostate cancer patients who have experienced biochemical relapse after radical ret... more A subgroup of prostate cancer patients who have experienced biochemical relapse after radical retropubic prostatectomy (RRP) can benefit from radiation therapy to the prostate fossa. These patients demonstrate biochemical relapse secondary to local failure in the absence of distant failure. In order to define this subgroup, we investigated the impact of pathological and biochemical variables and pre-radiation therapy biopsy of the prostate fossa on biochemical disease-free survival (bNED) and initial prostate-specific antigen response. Sixty-two patients with localized prostate cancer who had biochemical relapse after RRP were treated with post-RRP radiation therapy localized to the prostate fossa (median dose, 6120 cGy) and were subsequently followed up for a median time of 47 months. Cox regression analyses and Kaplan-Meier estimates for bNED were used to identify prognostic variables. The Fisher's exact test was used to test the interaction of initial prostate-specific antige...
In February 1999, the National Cancer Institute (NCI) issued a clinical alert based on five rando... more In February 1999, the National Cancer Institute (NCI) issued a clinical alert based on five randomized trials that reported better overall survival (OS) with concurrent chemoradiotherapy (CCRT) than with surgery or radiation alone for locoregional cervical cancer. This study analyzes data from the surveillance epidemiology and end results (SEER) program to evaluate the improvement in survival in the era of CCRT. The SEER database was queried for FIGO stages IB2-IVA cervical cancer patients treated with radiotherapy between 1995 and 2002. Patients diagnosed between 1999 and 2002 (CCRT era) were assumed to have received CCRT more frequently than patients diagnosed between 1995 and 1998 (RT era). Cases were stratified by period of diagnosis, age, and SEER region. OS and cause specific survival (CSS) were compared between the two time periods with chi-square log-rank tests. Multivariable Cox models were also used to compare OS and CSS between the two time periods, with adjustment for st...
Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients ... more Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients present with extensive stage of the disease. To reduce the high risk of brain metastases, prophylactic cranial irradiation has been shown to be very effective. Prophylactic cranial irradiation should now routinely be used for all patients who have responded to chemotherapy. Thoracic radiotherapy is often reserved for palliation. However, the high incidence of residual disease after chemotherapy and the reported beneficial effect of radiotherapy in a single study has led to two clinical trials which will soon open and address the question whether thoracic radiotherapy also has a role in responding patients with extensive stage small cell lung cancer.
A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediate... more A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in non-targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4 monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human monoclonal anti-CTLA-4 antibody) induced immune-mediated abscopal effects in poorly immunogenic pre-clinical tumor models and metastatic melanoma patients. However, no such reports exist for patients with metastatic lung adenocarcinoma. We report the first abscopal response in a treatment-refractory lung cancer patient treated with radiotherapy and ipilimumab. A post-treatment increase in tumor-infiltrating cytotoxic lymphocytes, tumor regression, and normalization of tumor markers was observed. One year after treatment with concurrent radiotherapy and ipilimumab the patient is without evidence of disease.
Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosi... more Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosis and resulting in a block of the cell cycle at G2 and M. The drug is isolated from the yew, Taxus sp. L., and is currently being evaluated in a series of Phase II and Phase III clinical trials. Taxol blocks cells in the most radiosensitive phases of the cell cycle and thus could act as a cell cycle-specific radiosensitizer. We report the results of combined taxol-radiation exposures in the human Grade III astrocytoma cell line, G18. Taxol is a potent inhibitor of G18 cell division; a concentration of 10 nM is cytostatic for a cell population observed for at least two doubling times. Cell survival curves for G18 cells showed a significant concentration-dependent interaction between taxol and radiation. Treatment of G18 cells with a fixed taxol concentration and radiation dose showed the interaction to be dependent on the duration of taxol exposure and consequently the fraction of cells i...
To evaluate the prognostic significance of prostate-specific antigen density (PSAD) in clinically... more To evaluate the prognostic significance of prostate-specific antigen density (PSAD) in clinically localized prostate cancer and determine whether this index is independent of or superior to prostate-specific antigen (PSA) in predicting outcome of patients treated with external beam radiotherapy. Between January 1989 and December 1993, 175 evaluable patients with clinically localized prostate cancer received definitive radiotherapy using computed tomography (CT)-guided conformal techniques. PSAD was defined as the ratio of the pretreatment serum PSA to the prostate volume measured from CT treatment planning scans by one investigator. All PSA values were determined using the Hybritech assay. Biochemical failure was defined as two consecutive elevations in PSA separated by at least 3 months and a final PSA value greater than 1 ng/mL. Multivariate analysis including PSA and Gleason score revealed both to be statistically significant predictors of biochemical disease-free survival (P = 0.048 and P < 0.001, respectively). PSAD did not achieve significance on regression analysis. A direct multivariate analysis including PSA and PSAD required dichotomization in order to reduce high correlation. This analysis demonstrated a relative risk (RR) for failure of 1.27 (NS) for high PSA versus low PSA compared with a RR of 1.20 (NS) for high PSAD versus low PSAD. A regression model containing all three variables indicated only the Gleason score as significant in predicting biochemical failure. These data do not suggest that PSAD is either an independent prognostic factor or a stronger discriminant of outcome than PSA in patients with clinically localized prostate cancer treated with definitive external beam radiotherapy. Larger patient numbers with longer follow-up data, use of a clinical end point, or an analysis restricted to the appropriate subgroup may demonstrate the utility of PSAD in the future.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, Jan 27, 2008
Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often... more Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast-cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study...
2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263), 2001
Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate... more Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy of prostate cancer. Yet no imaging modality, including B-mode images, reliably shows cancerous lesions of the prostate. Tissue-typing imaging based on spectrum analysis of ultrasonic radio-frequency (RF) echo signals may be able to overcome the limitations of conventional imaging modalities for visualizing
Medical Imaging 2004: Ultrasonic Imaging and Signal Processing, 2004
Our research is intended to develop ultrasonic methods for characterizing cancerous prostate tiss... more Our research is intended to develop ultrasonic methods for characterizing cancerous prostate tissue and thereby to improve the effectiveness of biopsy guidance, therapy targeting, and treatment monitoring. We acquired radio-frequency (RF) echo-signal data and clinical variables, e.g., PSA, during biopsy examinations. We computed spectra of the RF signals in each biopsied region, and trained neural network classifers with over 3,000
Breath testing could provide a rational tool for radiation biodosimetry because radiation causes ... more Breath testing could provide a rational tool for radiation biodosimetry because radiation causes distinct stress-producing molecular damage, notably an increased production of reactive oxygen species. The resulting oxidative stress accelerates lipid peroxidation of polyunsaturated fatty acids, liberating alkanes and alkane metabolites that are excreted in the breath as volatile organic compounds (VOCs). Breath tests were performed before and after radiation therapy over five days in 31 subjects receiving daily fractionated doses: 180-400 cGy d(-1) standard radiotherapy (n = 26), or 700-1200 cGy d(-1) high-dose stereotactic body radiotherapy (n = 5). Breath VOCs were assayed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Multiple Monte Carlo simulations identified approximately 50 VOCs as greater-than-chance biomarkers of radiation on all five days of the study. A consistent subset of 15 VOCs was observed at all time points. A radiation respo...
Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate... more Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning radiotherapy (i.e., brachytherapy and external-beam radiation) of prostate cancer (CaP). Yet B-mode images essentially do not allow visualization of cancerous lesions of the prostate. Ultrasonic tissue-typing imaging based on spectrum analysis of radio-frequency (RF) echo signals has shown promise for overcoming the limitations
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