S. Sarangkasiri - Academia.edu (original) (raw)
Papers by S. Sarangkasiri
International Journal of Radiation Oncology*Biology*Physics, 2016
International Journal of Radiation Oncology*Biology*Physics, 2016
Annals of Oncology, 2016
The effect of immunologic and targeted agents on intracranial response rates in patients with mel... more The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single session SRS and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. Patients were included if MBMs were treated with single session SRS within 3 months of receiving systemic therapy. The primary endpoint of this study was distant MBM control. Secondary endpoints were local MBM control defined as a >20% volume increase on follow up MRI, systemic progression free survival (sPFS), overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. Ninety-six patients were treated to 314 MBM over 119 SRS treatment sessions between 01/2007 and 08/2015. No significant differences were noted in age (p=0.27), gender (p=0.85), treated gross tumor volume (GTV) (p =0.26), or the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) (p =0.51) between the treatment cohorts. Twelve month KM distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (p =0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the Kaplan-Meier (KM) local MBM control rates amongst treatment groups, (p =0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared to conventional chemotherapy. In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.
International Journal of Radiation Oncology*Biology*Physics, 2015
International Journal of Radiation Oncology*Biology*Physics, 2015
International Journal of Radiation Oncology*Biology*Physics, 2014
International Journal of Radiation Oncology*Biology*Physics, 2014
Journal of Neuro-Oncology, 2014
Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) ... more Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) has been used as an alternative to single dose treatment for large cavities and to reduce risks of late toxicity. The purpose of this study was to evaluate the outcomes of patients treated with FSRT to the post-operative bed for both radioresistant and radiosensitive brain metastases. Between December 2009 and May 2013 a total of 65 patients with newly diagnosed brain metastases were treated with resection followed by FSRT. Patients were treated to a total dose of 20-30 Gy in five fractions. Median planning target volume (PTV) was 16.88 cm(3) (range 4.87-128.43 cm(3)). The median follow-up for all patients was 8.5 months (range 1.1-28.6 months) with a median of 12.9 months for living patients. One and two year Kaplan-Meier estimates of local control were 87.0 and 70.0 %, respectively. Local control at 1 year was 85.6 and 88.0% for radioresistant and radiosensitive tumors, respectively (p = 0.44). A PTV ≥17 cm(3), was associated with local failure, HR 8.63 ((1.44-164.78); p = 0.02). One and two year distant control rates were 50.9 and 46.2%, respectively with six patients (9.2%) experiencing leptomeningeal disease. OS rates at 1 and 2 years were 65.2 and 47.5%, respectively. Survival was significantly associated with recursive partitioning analysis class (p = 0.001) and graded prognostic assessment score (p = 0.005). One case of radionecrosis was noted on follow-up imaging. FSRT in five fractions offers excellent local control in both radiosensitive and radioresistant tumors with minimal toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2012
International Journal of Radiation Oncology*Biology*Physics, 2007
Background: To date, radiation oncologists at the H. Lee Moffitt Cancer Center and Research Insti... more Background: To date, radiation oncologists at the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL) have treated 29 patients with stereotactic radiotherapy (10 Gy  5 fractions) to peripheral lung tumors (SBRT), as well as 5 patients in standard fractionation (2 Gy  35 fractions) to small central lesions (IGRT). All were treated on a Novalis stereotactic treatment machine equipped with an ExacTrac Treatment Verification System (BrainLAB) for image-guided treatment delivery. The SBRT patients were immobilized using the BodyFix system (Medical Intelligence), while the standard fractionation patients were immobilized using VacLoc cradles (MedTec). The SBRT patients underwent bronchoscopic placement of gold Visicoil fiducials for target visualization. SBRT patients also underwent abdominal compression to minimize respiratory excursion. All patients were simulated on a 4D CT scanner (Phillips) and ITVs were generated to account for respiratory motion. PTV margins were at the discretion of the treating physician.
International Journal of Radiation Oncology*Biology*Physics, 2009
radiation therapy, capecitabine, and oxaliplatin for locally advanced rectal cancer. The trial is... more radiation therapy, capecitabine, and oxaliplatin for locally advanced rectal cancer. The trial is ongoing and we are reporting on the initial safety and efficacy of this regimen. Materials/Methods: Eligible patients had T3/T4 or node positive rectal adenocarcinoma. Patients received standard dose radiation therapy (50.4 Gy for 5.5 weeks) with concurrent capecitabine (825 mg/m2 PO q 12 hours M-F) oxaliplatin (50 mg/m2 i.v. once weekly) and Bevacizumab (5 mg/kg i.v. Days 1, 15, and 29). Following surgical resection, patients received adjuvant therapy consisting of 12 cycles of FOLFOX Q2 weeks (5-FU 400 mg/m2 i.v. bolus followed by 4,800 mg/m2 continuous infusion over 46 hours), Leucovorin(400 mg/m2 i.v.), oxaliplatin (85 mg/m2 i.v.), Bevacizumab (5 mg/kg day i.v.). The primary endpoint was pCR rate with secondary objectives resection type, overall survival, and toxicity. Results: Twenty-three patients have been enrolled and we are reporting toxicity data on the first 16 patients. Half of the patients reported worst Grade 3 and 4 toxicities in 6/16 (38%) and 2/16 (13%), respectively, consisting primarily of neutropenia, leucopenia, and diarrhea. One patient died during the third week of preoperative chemoradiation which was not felt to be treatment-related. Six patients (40%) did not receive their adjuvant chemotherapy within 8 weeks of surgery as mandated per protocol due to delayed wound healing. The mean time between the last Bevacizumab dose and surgery was 68 days, and the mean time to resuming chemotherapy after surgery was 49 days. Fifteen patients (94%) completed the entire preoperative chemoradiation regimen. Five of 15 patients (33%) had a pathologic complete response after preoperative chemoradiation with Bevacizumab. Conclusions: Bevacizumab given with preoperative capecitabine, oxaliplatin, and radiation for rectal cancer is associated with delayed wound healing. The pathologic complete response rate of 33% is encouraging. The study has been amended to extend the interval from surgery to initiate postoperative chemotherapy and Bevacizumab to 12 weeks.
International Journal of Radiation Oncology*Biology*Physics, 2009
respiration . 10 mm (2) presence of visible tumors on anterior-posterior X-ray films, (3) ability... more respiration . 10 mm (2) presence of visible tumors on anterior-posterior X-ray films, (3) ability to recognize visual information on the head-mounted display and to understand the purpose of this study, (4) ability to breath-hold comfortably for more than 10 s with inhaling oxygen, and (5) a willingness to participate in the study. The mean age was 72.5 years (range from 56 to 84 years). All patients were diagnosed with primary lung cancers. The motion range of the tumor centroid and diaphragm under shallow respiration was measured on the X-ray simulator. For monitoring the respiratory cycle, a commercially available high-speed machine vision system with a charge-coupled device camera was used. The vertical coordinate of the fiducial marker placed on the patient's abdomen was calculated by a pattern matching algorithm of the machine vision system. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so the breathing waveform would stay between the superimposed upper and lower threshold lines. Planning and treatment was performed under visual feedback-guided expiratory breath-holding. Irradiation per each port was performed during twice to five times breath-holds. Electronic portal images were obtained during treatment of coplanar ports. The cranial-caudal tumor position of the each image was measured manually on the console. The motion range of the tumor position during each single breath-hold was calculated as intrabreath-hold variability. The maximum displacement between the two to five averaged tumor positions of each single breath-hold was calculated as inter-breath-hold variability. Results: The mean range of cranial-caudal motion of the tumor and diaphragm was 13.5 mm, 17.0 mm, respectively. All eight patients well-tolerated the visual feedback-guided breath-hold maneuver. The sum of maximum of the inter-and intra-breathhold variability was 4.0 ± 1.8 mm (mean ± standard deviation). Conclusions: Visual feedback-guided breath-hold technique using a machine vision system with a charge-coupled device camera and a head-mounted display is feasible with relatively good reproducibility of the tumor position.
International Journal of Radiation Oncology*Biology*Physics, 2013
Few studies describe factors predictive of radiation pneumonitis in lung SBRT patients. We report... more Few studies describe factors predictive of radiation pneumonitis in lung SBRT patients. We report an analysis of 240 patients (263 isocenters) treated in 5-8 fractions. Female gender was predictive in univariable and multivariable analysis. In univariable analysis some dosimetric factors were predictive (V 5 , V 13 , V prescription [when dose Z 60 Gy]), as well as Charlson Comorbidity Index. However, in multivariable analysis dosimetric factors were eliminated; pack-years smoking and larger GITV and PTV were predictive.
International Journal of Radiation Oncology*Biology*Physics, 2011
Purpose/Objective(s): To assess the usefulness of monitoring serum AFP levels for predicting recu... more Purpose/Objective(s): To assess the usefulness of monitoring serum AFP levels for predicting recurrence pattern after carbonion radiotherapy. Materials/Methods: Between April 1995 and March 2003, 157 consecutive patients with histologically-proven hepatocellular carcinoma undergoing definitive carbon-ion radiotherapy entered this study. All tumors were recurrent or residual after other treatments or were not candidates for any other prospective study. During these periods, various protocols were employed, including 48 GyE in 4 fractions and 79.5 GyE in 15 fractions, after approval by the institutional review board. All patients signed an informed consent form. Serum AFP levels were measured before and at 3, 6, 12 and 18 months after treatment. Patterns of recurrence were categorized as local (in-field), intra-hepatic or distant. Associations between clinical/laboratory data including AFP, PIVKA-II, albumin, total bilirubin, platelet count, prothrombin time, indocyanine green retention rate at 15 min and Child-Pugh score and the onset of recurrence or distant metastasis were analyzed. Patients with AFP level .20 ng/ml before treatment were defined as AFP-positive. Results: Follow-up periods were 4.1-66 months (median 35.4 months). The 3-year survival rate for all 157 patients was 50%. In 97 AFP-positive cases, 12 developed intra-hepatic recurrence alone. Serum AFP levels of these 12 patients decreased to normal range initially, but in 7 of them, the AFP levels doubled at 12-18 months after treatment. In contrast, 3 cases developed local failure alone; AFP levels of these 3 cases did not fall to the normal level, and in 2 of them, the levels doubled at 3-6 months after treatment. In majority of cases with tumor recurrence, re-elevation of AFP levels was observed prior to its documentation by imaging studies. Thus, re-elevation of AFP levels tended to be observed earlier in patients developing in-filed recurrence. In 60 AFPnegative cases, 40 developed recurrence. AFP levels remained within normal range even after recurrence in 35 of the 40 cases. Regarding prognostic factors, AFP level .50 ng/ml and total bilirubin .1.6 mg/dl were associated with development of intrahepatic recurrence within 6 months, and AFP level .60 ng/ml and platelet count \70,000/mm 3 were associated with development of distant metastasis. Conclusions: AFP monitoring is useful to detect tumor recurrence in AFP-positive cases. Patterns of AFP change might be different between intra-hepatic failure and local failure. AFP .50 ng/ml and total bilirubin .1.6 mg/dl were predictive of development of intra-hepatic recurrence within 6 months. AFP .60 ng/ml and platelet \70,000/mm 3 were predictive of development of distant metastasis.
International Journal of Radiation Oncology*Biology*Physics, 2016
International Journal of Radiation Oncology*Biology*Physics, 2016
Annals of Oncology, 2016
The effect of immunologic and targeted agents on intracranial response rates in patients with mel... more The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single session SRS and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. Patients were included if MBMs were treated with single session SRS within 3 months of receiving systemic therapy. The primary endpoint of this study was distant MBM control. Secondary endpoints were local MBM control defined as a >20% volume increase on follow up MRI, systemic progression free survival (sPFS), overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. Ninety-six patients were treated to 314 MBM over 119 SRS treatment sessions between 01/2007 and 08/2015. No significant differences were noted in age (p=0.27), gender (p=0.85), treated gross tumor volume (GTV) (p =0.26), or the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) (p =0.51) between the treatment cohorts. Twelve month KM distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (p =0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the Kaplan-Meier (KM) local MBM control rates amongst treatment groups, (p =0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared to conventional chemotherapy. In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.
International Journal of Radiation Oncology*Biology*Physics, 2015
International Journal of Radiation Oncology*Biology*Physics, 2015
International Journal of Radiation Oncology*Biology*Physics, 2014
International Journal of Radiation Oncology*Biology*Physics, 2014
Journal of Neuro-Oncology, 2014
Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) ... more Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) has been used as an alternative to single dose treatment for large cavities and to reduce risks of late toxicity. The purpose of this study was to evaluate the outcomes of patients treated with FSRT to the post-operative bed for both radioresistant and radiosensitive brain metastases. Between December 2009 and May 2013 a total of 65 patients with newly diagnosed brain metastases were treated with resection followed by FSRT. Patients were treated to a total dose of 20-30 Gy in five fractions. Median planning target volume (PTV) was 16.88 cm(3) (range 4.87-128.43 cm(3)). The median follow-up for all patients was 8.5 months (range 1.1-28.6 months) with a median of 12.9 months for living patients. One and two year Kaplan-Meier estimates of local control were 87.0 and 70.0 %, respectively. Local control at 1 year was 85.6 and 88.0% for radioresistant and radiosensitive tumors, respectively (p = 0.44). A PTV ≥17 cm(3), was associated with local failure, HR 8.63 ((1.44-164.78); p = 0.02). One and two year distant control rates were 50.9 and 46.2%, respectively with six patients (9.2%) experiencing leptomeningeal disease. OS rates at 1 and 2 years were 65.2 and 47.5%, respectively. Survival was significantly associated with recursive partitioning analysis class (p = 0.001) and graded prognostic assessment score (p = 0.005). One case of radionecrosis was noted on follow-up imaging. FSRT in five fractions offers excellent local control in both radiosensitive and radioresistant tumors with minimal toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2012
International Journal of Radiation Oncology*Biology*Physics, 2007
Background: To date, radiation oncologists at the H. Lee Moffitt Cancer Center and Research Insti... more Background: To date, radiation oncologists at the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL) have treated 29 patients with stereotactic radiotherapy (10 Gy  5 fractions) to peripheral lung tumors (SBRT), as well as 5 patients in standard fractionation (2 Gy  35 fractions) to small central lesions (IGRT). All were treated on a Novalis stereotactic treatment machine equipped with an ExacTrac Treatment Verification System (BrainLAB) for image-guided treatment delivery. The SBRT patients were immobilized using the BodyFix system (Medical Intelligence), while the standard fractionation patients were immobilized using VacLoc cradles (MedTec). The SBRT patients underwent bronchoscopic placement of gold Visicoil fiducials for target visualization. SBRT patients also underwent abdominal compression to minimize respiratory excursion. All patients were simulated on a 4D CT scanner (Phillips) and ITVs were generated to account for respiratory motion. PTV margins were at the discretion of the treating physician.
International Journal of Radiation Oncology*Biology*Physics, 2009
radiation therapy, capecitabine, and oxaliplatin for locally advanced rectal cancer. The trial is... more radiation therapy, capecitabine, and oxaliplatin for locally advanced rectal cancer. The trial is ongoing and we are reporting on the initial safety and efficacy of this regimen. Materials/Methods: Eligible patients had T3/T4 or node positive rectal adenocarcinoma. Patients received standard dose radiation therapy (50.4 Gy for 5.5 weeks) with concurrent capecitabine (825 mg/m2 PO q 12 hours M-F) oxaliplatin (50 mg/m2 i.v. once weekly) and Bevacizumab (5 mg/kg i.v. Days 1, 15, and 29). Following surgical resection, patients received adjuvant therapy consisting of 12 cycles of FOLFOX Q2 weeks (5-FU 400 mg/m2 i.v. bolus followed by 4,800 mg/m2 continuous infusion over 46 hours), Leucovorin(400 mg/m2 i.v.), oxaliplatin (85 mg/m2 i.v.), Bevacizumab (5 mg/kg day i.v.). The primary endpoint was pCR rate with secondary objectives resection type, overall survival, and toxicity. Results: Twenty-three patients have been enrolled and we are reporting toxicity data on the first 16 patients. Half of the patients reported worst Grade 3 and 4 toxicities in 6/16 (38%) and 2/16 (13%), respectively, consisting primarily of neutropenia, leucopenia, and diarrhea. One patient died during the third week of preoperative chemoradiation which was not felt to be treatment-related. Six patients (40%) did not receive their adjuvant chemotherapy within 8 weeks of surgery as mandated per protocol due to delayed wound healing. The mean time between the last Bevacizumab dose and surgery was 68 days, and the mean time to resuming chemotherapy after surgery was 49 days. Fifteen patients (94%) completed the entire preoperative chemoradiation regimen. Five of 15 patients (33%) had a pathologic complete response after preoperative chemoradiation with Bevacizumab. Conclusions: Bevacizumab given with preoperative capecitabine, oxaliplatin, and radiation for rectal cancer is associated with delayed wound healing. The pathologic complete response rate of 33% is encouraging. The study has been amended to extend the interval from surgery to initiate postoperative chemotherapy and Bevacizumab to 12 weeks.
International Journal of Radiation Oncology*Biology*Physics, 2009
respiration . 10 mm (2) presence of visible tumors on anterior-posterior X-ray films, (3) ability... more respiration . 10 mm (2) presence of visible tumors on anterior-posterior X-ray films, (3) ability to recognize visual information on the head-mounted display and to understand the purpose of this study, (4) ability to breath-hold comfortably for more than 10 s with inhaling oxygen, and (5) a willingness to participate in the study. The mean age was 72.5 years (range from 56 to 84 years). All patients were diagnosed with primary lung cancers. The motion range of the tumor centroid and diaphragm under shallow respiration was measured on the X-ray simulator. For monitoring the respiratory cycle, a commercially available high-speed machine vision system with a charge-coupled device camera was used. The vertical coordinate of the fiducial marker placed on the patient's abdomen was calculated by a pattern matching algorithm of the machine vision system. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so the breathing waveform would stay between the superimposed upper and lower threshold lines. Planning and treatment was performed under visual feedback-guided expiratory breath-holding. Irradiation per each port was performed during twice to five times breath-holds. Electronic portal images were obtained during treatment of coplanar ports. The cranial-caudal tumor position of the each image was measured manually on the console. The motion range of the tumor position during each single breath-hold was calculated as intrabreath-hold variability. The maximum displacement between the two to five averaged tumor positions of each single breath-hold was calculated as inter-breath-hold variability. Results: The mean range of cranial-caudal motion of the tumor and diaphragm was 13.5 mm, 17.0 mm, respectively. All eight patients well-tolerated the visual feedback-guided breath-hold maneuver. The sum of maximum of the inter-and intra-breathhold variability was 4.0 ± 1.8 mm (mean ± standard deviation). Conclusions: Visual feedback-guided breath-hold technique using a machine vision system with a charge-coupled device camera and a head-mounted display is feasible with relatively good reproducibility of the tumor position.
International Journal of Radiation Oncology*Biology*Physics, 2013
Few studies describe factors predictive of radiation pneumonitis in lung SBRT patients. We report... more Few studies describe factors predictive of radiation pneumonitis in lung SBRT patients. We report an analysis of 240 patients (263 isocenters) treated in 5-8 fractions. Female gender was predictive in univariable and multivariable analysis. In univariable analysis some dosimetric factors were predictive (V 5 , V 13 , V prescription [when dose Z 60 Gy]), as well as Charlson Comorbidity Index. However, in multivariable analysis dosimetric factors were eliminated; pack-years smoking and larger GITV and PTV were predictive.
International Journal of Radiation Oncology*Biology*Physics, 2011
Purpose/Objective(s): To assess the usefulness of monitoring serum AFP levels for predicting recu... more Purpose/Objective(s): To assess the usefulness of monitoring serum AFP levels for predicting recurrence pattern after carbonion radiotherapy. Materials/Methods: Between April 1995 and March 2003, 157 consecutive patients with histologically-proven hepatocellular carcinoma undergoing definitive carbon-ion radiotherapy entered this study. All tumors were recurrent or residual after other treatments or were not candidates for any other prospective study. During these periods, various protocols were employed, including 48 GyE in 4 fractions and 79.5 GyE in 15 fractions, after approval by the institutional review board. All patients signed an informed consent form. Serum AFP levels were measured before and at 3, 6, 12 and 18 months after treatment. Patterns of recurrence were categorized as local (in-field), intra-hepatic or distant. Associations between clinical/laboratory data including AFP, PIVKA-II, albumin, total bilirubin, platelet count, prothrombin time, indocyanine green retention rate at 15 min and Child-Pugh score and the onset of recurrence or distant metastasis were analyzed. Patients with AFP level .20 ng/ml before treatment were defined as AFP-positive. Results: Follow-up periods were 4.1-66 months (median 35.4 months). The 3-year survival rate for all 157 patients was 50%. In 97 AFP-positive cases, 12 developed intra-hepatic recurrence alone. Serum AFP levels of these 12 patients decreased to normal range initially, but in 7 of them, the AFP levels doubled at 12-18 months after treatment. In contrast, 3 cases developed local failure alone; AFP levels of these 3 cases did not fall to the normal level, and in 2 of them, the levels doubled at 3-6 months after treatment. In majority of cases with tumor recurrence, re-elevation of AFP levels was observed prior to its documentation by imaging studies. Thus, re-elevation of AFP levels tended to be observed earlier in patients developing in-filed recurrence. In 60 AFPnegative cases, 40 developed recurrence. AFP levels remained within normal range even after recurrence in 35 of the 40 cases. Regarding prognostic factors, AFP level .50 ng/ml and total bilirubin .1.6 mg/dl were associated with development of intrahepatic recurrence within 6 months, and AFP level .60 ng/ml and platelet count \70,000/mm 3 were associated with development of distant metastasis. Conclusions: AFP monitoring is useful to detect tumor recurrence in AFP-positive cases. Patterns of AFP change might be different between intra-hepatic failure and local failure. AFP .50 ng/ml and total bilirubin .1.6 mg/dl were predictive of development of intra-hepatic recurrence within 6 months. AFP .60 ng/ml and platelet \70,000/mm 3 were predictive of development of distant metastasis.