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Prospective Analysis of Breast Cancer Associated Lymphedema: Utilizing Natural History to Inform Volumetric Thresholds for Intervention
Proceedings of the 51st Annual ASTRO Meeting
236
A Phase I Trial of the HIV Protease Inhibitor Nelfinavir with Concurrent Chemoradiotherapy (CT-RT) for Stage IIIA/IIIB NSCLC: A Report of Toxicities and Metabolic Response
R. Rengan1, R. Mick1, D. Pryma1, L. Lin1, A. Maity1, A. Gupta2, T. Evans1, J. Stevenson1, C. J. Langer1, S. M. Hahn1, et al. 1
University of Pennsylvania, Philadelphia, PA, 2University of Iowa, Iowa City, IA
Purpose/Objective(s): Preclinical studies have shown that HIV protease inhibitors can radiosensitize cells in vitro and in vivo. The objective of this Phase I trial was to determine dose-limiting toxicities and maximally tolerated dose of Nelfinavir in combination with concurrent CT-RT in locally advanced non–small-cell lung cancer (NSCLC). The secondary endpoint was metabolic response as determined by post-treatment PET/CT at three months after completion of therapy. Materials/Methods: Nelfinavir (doses 625 mg p.o. b.i.d., 1,250 mg p.o. b.i.d.) was administered for 7 to 14 days prior to and concurrently with concurrent CT-RT to patients with biopsy-confirmed Phase IIIA or IIIB inoperable NSCLC. Five patients were treated at 625 mg p.o. b.i.d.; 7 patients were treated at 1,250 mg p.o. b.i.d.. Patients were treated with concurrent cisplatin and etoposide with thoracic radiotherapy to a definitive dose of 60–66.6 Gy in 180 cGy fractions. The DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or nonhematologic Grade 3 or higher toxicity except esophagitis and pneumonitis. Metabolic response of the primary tumor on PET was scored by published criteria. Results: Sixteen patients were enrolled and 12 patients were treated with nelfinavir and concurrent chemoradiotherapy. Two patients were excluded due to identification of metastatic disease during eligibility screening. One patient provided consent and then withdrew prior to initiation of nelfinavir. One patient withdrew after 2 days of nelfinavir prior to initiating chemoradiotherapy due to anxiety, but was followed for DLT and is included in the toxicity analysis. No DLTs have been observed at either dose level. Two patients experienced Grade 4 neutropenia at Weeks 3 and 8. One patient experienced Grade 4 thrombocytopenia at Week 8. No other Grade 4 toxicities were observed. No dose-limiting esophagitis or pneumonitis was observed. Median follow-up for survivors is 7.5 months (range, 3–17 months). Of the 12 patients who received treatment 3 have died; 2 with distant progression, 1 without disease progression of a probable pulmonary embolus. One patient experienced local and regional progression at 9 months. Nine of the initial 12 patients had evaluable post-treatment PET/CT at 3 months after completion of therapy with response as follows: Overall response: 9/9 (100%); Complete metabolic response: 5/9 (56%); partial metabolic response 4/9 (44%). Conclusions: Nelfinavir administered with concurrent CT-RT at a dose of 1,250 mg p.o. b.i.d. is associated with acceptable toxicity in Stage IIIA/IIIB NSCLC. The metabolic response data suggest that nelfinavir has promising activity in patients with locally advanced NSCLC without a dose-dependent increase in chemoradiotherapy-associated toxicities. Author Disclosure: R. Rengan, None; R. Mick, None; D. Pryma, None; L. Lin, None; A. Maity, None; A. Gupta, Patent submission pending for nelfinavir (did not contribute to data analysis or performance of any component of this trial.), E. Ownership Interest; T. Evans, None; J. Stevenson, None; C.J. Langer, None; S.M. Hahn, None.
237
Prospective Analysis of Breast Cancer Associated Lymphedema: Utilizing Natural History to Inform Volumetric Thresholds for Intervention
T. A. Russell, J. O’Toole, M. Ancukiewicz, M. Singer, R. Abi Raad, M. Specht, B. L. Smith, A. G. Taghian Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Breast Cancer Associated Lymphedema (BCAL) is known to have a detrimental effect on quality of life, body image, and upper extremity function. Risk factors include axillary surgery and/or radiation and a BMI .35. Recent research has advocated for early intervention with a compression sleeve at a 3% increase in arm volume, yet there is little evidence to support this recommendation. The goal of this study is to assess the natural history of BCAL and define potential thresholds for intervention by analyzing prospective, longitudinal arm volume measurements of women with primary breast cancer (PBC). Materials/Methods: Since 2005, a longitudinal BCAL screening program has been instituted at Massachusetts General Hospital. Women are screened with a Perometer (Pero-System), an infrared light volumeter, throughout treatment and follow-up. For this analysis, only unilateral PBC patients with $3 Perometer measurements and $3 months of follow-up postsurgery are included. Arm volume changes at a given time point (TX) are quantified as Relative Volume Change (RVC) between the treated (T) and nontreated (N) arm as compared to the baseline (preoperative) measurement (T1): RVC = (Ttx/Ntx)/(Tt1/Nt1)-1. The sequela of arm volume after reaching $3%, $5% or $10% RVC was evaluated by review of measurement data. The BCAL is defined as: \3% Baseline, 3–5% Pre-Clinical, 5–10% Mild, 10–15% Moderate, and .15% Severe. Results: A total of 1,279 patients were screened prospectively with the Perometer, 1,071 had a baseline measurement and 528 met the research criteria. Median number of measurements was 4 and median follow-up postoperatively was 14 months. Respectively, 34.3% (n = 181), 14% (74), and 2.8% (15) of patients reached the 3%, 5%, and 10% thresholds. After reaching the 3%, 5%, and 10% RVC thresholds: 79.6%, 52.9%, and 20.0% returned to baseline or preclinical RVC, 13.8%, 36.8%, and 0% exhibited mild edema, and 6.7%, 19.1%, and 53.3% progressed to moderate or severe edema by the end of follow-up, respectively. Conclusions: The natural history of BCAL varies throughout the course of treatment and follow-up. Prospective, longitudinal screening that begins preoperatively is pertinent to evaluate early signs of BCAL. Once an increase in arm volume is identified, it is evident that an intervention at 3% RVC places an undue burden on patients due to their low risk of progression. Furthermore, in light of the higher risk of progression, a 5% threshold may be considered for increased surveillance or intervention, and 10% for intervention and symptom management. Additional research through a randomized control trial is necessary to further define evidence based guidelines for BCAL interventions. Author Disclosure: T.A. Russell, None; J. O’Toole, None; M. Ancukiewicz, None; M. Singer, None; R. Abi Raad, None; M. Specht, None; B.L. Smith, None; A.G. Taghian, None.
238
Sexual Function after Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial
E. A. Wiegner, C. R. King Stanford University, Stanford, CA Purpose/Objective(s): To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT).
S111
236
A Phase I Trial of the HIV Protease Inhibitor Nelfinavir with Concurrent Chemoradiotherapy (CT-RT) for Stage IIIA/IIIB NSCLC: A Report of Toxicities and Metabolic Response
R. Rengan1, R. Mick1, D. Pryma1, L. Lin1, A. Maity1, A. Gupta2, T. Evans1, J. Stevenson1, C. J. Langer1, S. M. Hahn1, et al. 1
University of Pennsylvania, Philadelphia, PA, 2University of Iowa, Iowa City, IA
Purpose/Objective(s): Preclinical studies have shown that HIV protease inhibitors can radiosensitize cells in vitro and in vivo. The objective of this Phase I trial was to determine dose-limiting toxicities and maximally tolerated dose of Nelfinavir in combination with concurrent CT-RT in locally advanced non–small-cell lung cancer (NSCLC). The secondary endpoint was metabolic response as determined by post-treatment PET/CT at three months after completion of therapy. Materials/Methods: Nelfinavir (doses 625 mg p.o. b.i.d., 1,250 mg p.o. b.i.d.) was administered for 7 to 14 days prior to and concurrently with concurrent CT-RT to patients with biopsy-confirmed Phase IIIA or IIIB inoperable NSCLC. Five patients were treated at 625 mg p.o. b.i.d.; 7 patients were treated at 1,250 mg p.o. b.i.d.. Patients were treated with concurrent cisplatin and etoposide with thoracic radiotherapy to a definitive dose of 60–66.6 Gy in 180 cGy fractions. The DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or nonhematologic Grade 3 or higher toxicity except esophagitis and pneumonitis. Metabolic response of the primary tumor on PET was scored by published criteria. Results: Sixteen patients were enrolled and 12 patients were treated with nelfinavir and concurrent chemoradiotherapy. Two patients were excluded due to identification of metastatic disease during eligibility screening. One patient provided consent and then withdrew prior to initiation of nelfinavir. One patient withdrew after 2 days of nelfinavir prior to initiating chemoradiotherapy due to anxiety, but was followed for DLT and is included in the toxicity analysis. No DLTs have been observed at either dose level. Two patients experienced Grade 4 neutropenia at Weeks 3 and 8. One patient experienced Grade 4 thrombocytopenia at Week 8. No other Grade 4 toxicities were observed. No dose-limiting esophagitis or pneumonitis was observed. Median follow-up for survivors is 7.5 months (range, 3–17 months). Of the 12 patients who received treatment 3 have died; 2 with distant progression, 1 without disease progression of a probable pulmonary embolus. One patient experienced local and regional progression at 9 months. Nine of the initial 12 patients had evaluable post-treatment PET/CT at 3 months after completion of therapy with response as follows: Overall response: 9/9 (100%); Complete metabolic response: 5/9 (56%); partial metabolic response 4/9 (44%). Conclusions: Nelfinavir administered with concurrent CT-RT at a dose of 1,250 mg p.o. b.i.d. is associated with acceptable toxicity in Stage IIIA/IIIB NSCLC. The metabolic response data suggest that nelfinavir has promising activity in patients with locally advanced NSCLC without a dose-dependent increase in chemoradiotherapy-associated toxicities. Author Disclosure: R. Rengan, None; R. Mick, None; D. Pryma, None; L. Lin, None; A. Maity, None; A. Gupta, Patent submission pending for nelfinavir (did not contribute to data analysis or performance of any component of this trial.), E. Ownership Interest; T. Evans, None; J. Stevenson, None; C.J. Langer, None; S.M. Hahn, None.
237
Prospective Analysis of Breast Cancer Associated Lymphedema: Utilizing Natural History to Inform Volumetric Thresholds for Intervention
T. A. Russell, J. O’Toole, M. Ancukiewicz, M. Singer, R. Abi Raad, M. Specht, B. L. Smith, A. G. Taghian Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Breast Cancer Associated Lymphedema (BCAL) is known to have a detrimental effect on quality of life, body image, and upper extremity function. Risk factors include axillary surgery and/or radiation and a BMI .35. Recent research has advocated for early intervention with a compression sleeve at a 3% increase in arm volume, yet there is little evidence to support this recommendation. The goal of this study is to assess the natural history of BCAL and define potential thresholds for intervention by analyzing prospective, longitudinal arm volume measurements of women with primary breast cancer (PBC). Materials/Methods: Since 2005, a longitudinal BCAL screening program has been instituted at Massachusetts General Hospital. Women are screened with a Perometer (Pero-System), an infrared light volumeter, throughout treatment and follow-up. For this analysis, only unilateral PBC patients with $3 Perometer measurements and $3 months of follow-up postsurgery are included. Arm volume changes at a given time point (TX) are quantified as Relative Volume Change (RVC) between the treated (T) and nontreated (N) arm as compared to the baseline (preoperative) measurement (T1): RVC = (Ttx/Ntx)/(Tt1/Nt1)-1. The sequela of arm volume after reaching $3%, $5% or $10% RVC was evaluated by review of measurement data. The BCAL is defined as: \3% Baseline, 3–5% Pre-Clinical, 5–10% Mild, 10–15% Moderate, and .15% Severe. Results: A total of 1,279 patients were screened prospectively with the Perometer, 1,071 had a baseline measurement and 528 met the research criteria. Median number of measurements was 4 and median follow-up postoperatively was 14 months. Respectively, 34.3% (n = 181), 14% (74), and 2.8% (15) of patients reached the 3%, 5%, and 10% thresholds. After reaching the 3%, 5%, and 10% RVC thresholds: 79.6%, 52.9%, and 20.0% returned to baseline or preclinical RVC, 13.8%, 36.8%, and 0% exhibited mild edema, and 6.7%, 19.1%, and 53.3% progressed to moderate or severe edema by the end of follow-up, respectively. Conclusions: The natural history of BCAL varies throughout the course of treatment and follow-up. Prospective, longitudinal screening that begins preoperatively is pertinent to evaluate early signs of BCAL. Once an increase in arm volume is identified, it is evident that an intervention at 3% RVC places an undue burden on patients due to their low risk of progression. Furthermore, in light of the higher risk of progression, a 5% threshold may be considered for increased surveillance or intervention, and 10% for intervention and symptom management. Additional research through a randomized control trial is necessary to further define evidence based guidelines for BCAL interventions. Author Disclosure: T.A. Russell, None; J. O’Toole, None; M. Ancukiewicz, None; M. Singer, None; R. Abi Raad, None; M. Specht, None; B.L. Smith, None; A.G. Taghian, None.
238
Sexual Function after Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial
E. A. Wiegner, C. R. King Stanford University, Stanford, CA Purpose/Objective(s): To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT).
S111