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Proton Radiation Therapy and the Incidence of Secondary Malignancies
I. J. Radiation Oncology d Biology d Physics
S178
1074
Volume 69, Number 3, Supplement, 2007
Comparison of 7-Year Outcomes Between LDR Brachytherapy and High Dose IMRT for Patients With Clinically Localized Prostate Cancer
M. J. Zelefsky, Y. Yamada, M. Hunt, G. N. Cohen, A. M. Shippy, M. Zaider Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): To compare the 7-year PSA relapse-free survival outcome and incidence of toxicity for patients with prostate cancer treated with I-125 brachytherapy delivered with real-time intraoperative planning (BRT) and high-dose intensity modulated external beam radiotherapy (IMRT). Materials/Methods: Between January 1998 and May 2002, 1126 consecutive patients with low and intermediate risk prostate cancer, were treated with BRT (n = 421) and IMRT (n = 705). The median dose for the BRT group was 144 Gy and the median RT dose in the IMRT group was 81 Gy. The median ages in the BRT and IMRT groups were 66 and 69 years, respectively. Neoadjuvant androgen deprivation therapy usage were less prevalent for BRT compared to IMRT treated patients (36% for BRT and 46% for IMRT; p = 0.001). PSA relapse was defined according to the nadir +2 definition, and late toxicity was classified according to NCI’s Common Terminology Criteria for Adverse Events (version 3.0). The median follow-up times in the BRT and IMRT groups were 59 and 66 months, respectively. Results: Among low risk patients (n = 672), the 7-year PSA relapse-free survival outcome for the BRT group was 98% compared to 88% for IMRT patients (p \ 0.001). Among intermediate risk patients (n = 454), the 7-year PSA relapse-free survival outcome for the BRT group was 93% compared to 74% for the IMRT patients (p = 0.08). Cox regression analysis demonstrated that the following variables were predictors of improved biochemical tumor control: BRT vs IMRT (p \ 0.001 hazard ratio (HR) 4.9); stage T1c vs T2 (p = 0.094 - hazard ratio 1.94); Gleason # 6 vs 7 (p \ 0.01 - HR 2.51) PSA (# 6.5 vs . 6.5 (p \ 0.01 HR 2.23) and neo adjuvant-androgen deprivation: (p = 0.5 - HR 0.86). Late grade 2 GI toxicities were observed in 6% and 2% of the BRT and IMRT groups, respectively (p = 0.0002). There were no significant differences between the treatment groups for late grade 3 or greater GI complications (1% and \1% of the BRT and IMRT groups, respectively; p = 0.14). Late grade 2 GU toxicities were more often observed for BRT compared to the IMRT group (18% and 7%), respectively (p \ 0.001). There were no significant differences between the treatment groups for late grade 3 urinary symptoms (3% and 2% of the BRT and IMRT groups, respectively; p = 0.27). Conclusions: Especially for low risk patients, biochemical tumor control is superior for patients treated with BRT compared to high dose IMRT. While significant toxicities were similarly minimal for both treatment groups, a modest, but significant, increase in grade 2 urinary and rectal symptoms was noted in the BRT group compared to IMRT treated patients. Author Disclosure: M.J. Zelefsky, None; Y. Yamada, None; M. Hunt, None; G.N. Cohen, None; A.M. Shippy, None; M. Zaider, None.
1075
Proton Radiation Therapy and the Incidence of Secondary Malignancies
C. S. Chung1, T. Yock2, J. Johnson2, B. Esty2, N. Tarbell2 1
Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA
Background: Advances in cancer therapy have significantly improved survival rates, but have increased concerns about late effects, including secondary malignancies. In comparison with standard photon therapy, proton radiation decreases radiation to adjacent normal tissues. However, scatter neutron production may contribute to the risk of secondary malignancies. Purpose/Objective(s): To calculate the incidence of second malignancies in patients treated with proton radiation therapy. Materials/Methods: We identified 1,450 patients treated with proton radiation therapy from 1974–2001 at the Harvard Cyclotron in Cambridge, MA. The study was restricted to patients with $5 years of follow-up. Patients receiving therapy to the eye were excluded. Data was abstracted from relevant charts and scripted telephone follow-up was conducted. Mortality data was obtained from the National Death Index. Results: 647 patients had $5 years of follow-up, yielding 6,893 person-years of follow-up. 329 patients (51%) were treated for a primary tumor of the CNS or skull base. 88 patients (14%) had a primary cancer of the head or neck. Median duration of follow-up was 107 months. Median overall survival was 180 months [95% CI 158, 206]. The average age at radiation therapy was 52.5 years [range 1, 88]. 47 patients (7.3%) developed second malignancies at a median of 5.3 years after treatment. 7 patients (1.1%) developed secondary malignancies within the prior proton radiation treatment field, and 3 patients (0.46%) developed three malignancies. Second malignancies included 40 solid tumors, 2 acute leukemias, and 5 lymphomas. All patients who developed second malignancies received mixed proton-photon therapy. The incidence rate of second malignancies was 63, 62, 54, and 82 cancers per 10,000 person-years for patients with a primary cancer of the head and neck, CNS, base of skull, or prostate, respectively. No secondary malignancies were observed in 15 pediatric patients (Table). Conclusions: A low rate of second malignancies was observed after proton radiation therapy, although further follow-up is required. The contribution of chemotherapeutic agents and photon therapy to this risk of second cancer requires further investigation.
Proceedings of the 49th Annual ASTRO Meeting
Site of second malignancy Brain
Lung/Mediastinum
Breast Colon Duodenum Stomach Prostate Bladder Uterus Sino-nasal/Nasopharynx Soft tissue
Bone Skin Lymphoma Leukemia
S179
Observed Incidence
Histology
4 2 1 5 1 1 3 2 1 1 1 3 1 1 2 1 1 1 1 6 1 5 2
Glioblastoma multiforme Schwannoma Meningioma Non-small cell carcinoma Small cell carcinoma Teratoma Adenocarcinoma Adenocarcinoma Adenoid cystic carcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Transitional cell carcinoma Adenocarcinoma Squamous cell carcinoma Liposarcoma (retroperitoneal) Desmoid (chest wall) Malignant fibrous histiocytoma (sacrum) Squamous cell carcinoma (temporal bone) Squamous cell carcinoma Malignant melanoma Lymphoma Leukemia
Author Disclosure: C.S. Chung, None; T. Yock, None; J. Johnson, None; B. Esty, None; N. Tarbell, None.
1076
Adverse Impact of Mucositis on Health Related Quality of Life Outcomes and Resource use in Head and Neck Cancer Patients Receiving Radiation
A. S. Garden1, R. B. Tishler2, A. Barasch3, M. T. Brennan4, P. M. Harari5, M. R. Kudrimoti6, C. J. Schultz7, D. G. Brachman8, M. Vera-Llonch9, D. Keefe10 1 M.D. Anderson Cancer Center, Houston, TX, 2Dana Farber Cancer Institute, Boston, MA, 3The University of Alabama at Birmingham, Birmingham, AL, 4Carolinas Medical Center, Charlotte, NC, 5University of Wisconsin Cancer Center, Madison, WI, 6University of Kentucky, Lexington, KY, 7Medical College of Wisconsin, Milwaukee, WI, 8St. Josephs Hospital, Phoenix, AZ, 9 Policy Analysis, Inc., Brookline, MA, 10Royal Adelaide Hospital, North Terrace, SA, Australia
Background: The negative impact of oral mucositis (OM) caused by radiation therapy (RT) for head and neck cancers (HNC) on health, economic and quality of life (QoL) outcomes has been reported in retrospective studies, but it is likely that these underestimate OM’s true influence on resource use and QoL. We report interim results of a prospective observational study to estimate OM’s impact more accurately. Materials/Methods: Patients (pts) with oral cavity, oropharynx, hypopharynx (H), or larynx (L) cancers were enrolled prior to RT at 44 international centers. At baseline and daily thereafter, pts completed the OMDQ, a validated questionnaire that measures mouth and throat soreness (MTS), and overall health (OH). Pts scored MTS on a scale of 0 (‘‘none’’) to 4 (‘‘extreme’’) soreness and OH, from 0 (‘‘worst possible’’) to 10 (‘‘perfect’’) health. Pts completed the FACT-E, a validated QoL instrument, weekly, including its functional wellbeing (FWB) subscale. To describe resource use, pts were categorized by peak MTS score during RT. The relationships between paired, same day self-reports of MTS and OH, FACT-E, or FWB scores were described as means; standard errors were corrected for within-pt correlation using random effects linear regression. Mean scores were adjusted for baseline ECOG performance status (PS), chemotherapy (ctx) use, and cancer site. Results: 94 of a planned 270 pts have completed RT. 72% were males, 95% had good ECOG (0 or 1) PS status at baseline, and their mean age was 55 yrs. 25 (27%) pts had L or HP cancers, 67 (71%) received IMRT, and 56 (60%) received ctx. 100% of pts reported MTS at some time during RT; in 85%, the peak MTS was rated 3 or 4. 28% (95% CI: 18%–39%) of pts with peak MTS scores of 3– 4 required non-prophylactic gastrostomy tube insertion compared with 7% (95% CI: 0%–34%) of pts with peak MTS scores of 0–2. Similar findings (in pts with high and low MTS scores, respectively) were observed for hospitalization, 19% (95% CI: 11%–29%) vs 14% (95% CI: 2%–43%), and for Emergency Room (ER) visits, 15% (95% CI: 8%–25%) vs 7% (95% CI: 0%–34%). Pts reported high OH, QoL, and FWB when little or no MTS was present. But OH, QoL, and FWB decreased as MTS increased (See table). Conclusions: All pts with HNC report MTS during RT. Pts who report the highest peak MTS scores use more costly resources (ER and hospital visits, gastrostomy tubes) and report poorer OH, QoL, and FWB than previously described. These findings illustrate the need for interventions to prevent OM. Relationship between MTS and 726 paired, same-day reports of OH, QoL, and FWB in 94 pts.
S178
1074
Volume 69, Number 3, Supplement, 2007
Comparison of 7-Year Outcomes Between LDR Brachytherapy and High Dose IMRT for Patients With Clinically Localized Prostate Cancer
M. J. Zelefsky, Y. Yamada, M. Hunt, G. N. Cohen, A. M. Shippy, M. Zaider Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): To compare the 7-year PSA relapse-free survival outcome and incidence of toxicity for patients with prostate cancer treated with I-125 brachytherapy delivered with real-time intraoperative planning (BRT) and high-dose intensity modulated external beam radiotherapy (IMRT). Materials/Methods: Between January 1998 and May 2002, 1126 consecutive patients with low and intermediate risk prostate cancer, were treated with BRT (n = 421) and IMRT (n = 705). The median dose for the BRT group was 144 Gy and the median RT dose in the IMRT group was 81 Gy. The median ages in the BRT and IMRT groups were 66 and 69 years, respectively. Neoadjuvant androgen deprivation therapy usage were less prevalent for BRT compared to IMRT treated patients (36% for BRT and 46% for IMRT; p = 0.001). PSA relapse was defined according to the nadir +2 definition, and late toxicity was classified according to NCI’s Common Terminology Criteria for Adverse Events (version 3.0). The median follow-up times in the BRT and IMRT groups were 59 and 66 months, respectively. Results: Among low risk patients (n = 672), the 7-year PSA relapse-free survival outcome for the BRT group was 98% compared to 88% for IMRT patients (p \ 0.001). Among intermediate risk patients (n = 454), the 7-year PSA relapse-free survival outcome for the BRT group was 93% compared to 74% for the IMRT patients (p = 0.08). Cox regression analysis demonstrated that the following variables were predictors of improved biochemical tumor control: BRT vs IMRT (p \ 0.001 hazard ratio (HR) 4.9); stage T1c vs T2 (p = 0.094 - hazard ratio 1.94); Gleason # 6 vs 7 (p \ 0.01 - HR 2.51) PSA (# 6.5 vs . 6.5 (p \ 0.01 HR 2.23) and neo adjuvant-androgen deprivation: (p = 0.5 - HR 0.86). Late grade 2 GI toxicities were observed in 6% and 2% of the BRT and IMRT groups, respectively (p = 0.0002). There were no significant differences between the treatment groups for late grade 3 or greater GI complications (1% and \1% of the BRT and IMRT groups, respectively; p = 0.14). Late grade 2 GU toxicities were more often observed for BRT compared to the IMRT group (18% and 7%), respectively (p \ 0.001). There were no significant differences between the treatment groups for late grade 3 urinary symptoms (3% and 2% of the BRT and IMRT groups, respectively; p = 0.27). Conclusions: Especially for low risk patients, biochemical tumor control is superior for patients treated with BRT compared to high dose IMRT. While significant toxicities were similarly minimal for both treatment groups, a modest, but significant, increase in grade 2 urinary and rectal symptoms was noted in the BRT group compared to IMRT treated patients. Author Disclosure: M.J. Zelefsky, None; Y. Yamada, None; M. Hunt, None; G.N. Cohen, None; A.M. Shippy, None; M. Zaider, None.
1075
Proton Radiation Therapy and the Incidence of Secondary Malignancies
C. S. Chung1, T. Yock2, J. Johnson2, B. Esty2, N. Tarbell2 1
Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA
Background: Advances in cancer therapy have significantly improved survival rates, but have increased concerns about late effects, including secondary malignancies. In comparison with standard photon therapy, proton radiation decreases radiation to adjacent normal tissues. However, scatter neutron production may contribute to the risk of secondary malignancies. Purpose/Objective(s): To calculate the incidence of second malignancies in patients treated with proton radiation therapy. Materials/Methods: We identified 1,450 patients treated with proton radiation therapy from 1974–2001 at the Harvard Cyclotron in Cambridge, MA. The study was restricted to patients with $5 years of follow-up. Patients receiving therapy to the eye were excluded. Data was abstracted from relevant charts and scripted telephone follow-up was conducted. Mortality data was obtained from the National Death Index. Results: 647 patients had $5 years of follow-up, yielding 6,893 person-years of follow-up. 329 patients (51%) were treated for a primary tumor of the CNS or skull base. 88 patients (14%) had a primary cancer of the head or neck. Median duration of follow-up was 107 months. Median overall survival was 180 months [95% CI 158, 206]. The average age at radiation therapy was 52.5 years [range 1, 88]. 47 patients (7.3%) developed second malignancies at a median of 5.3 years after treatment. 7 patients (1.1%) developed secondary malignancies within the prior proton radiation treatment field, and 3 patients (0.46%) developed three malignancies. Second malignancies included 40 solid tumors, 2 acute leukemias, and 5 lymphomas. All patients who developed second malignancies received mixed proton-photon therapy. The incidence rate of second malignancies was 63, 62, 54, and 82 cancers per 10,000 person-years for patients with a primary cancer of the head and neck, CNS, base of skull, or prostate, respectively. No secondary malignancies were observed in 15 pediatric patients (Table). Conclusions: A low rate of second malignancies was observed after proton radiation therapy, although further follow-up is required. The contribution of chemotherapeutic agents and photon therapy to this risk of second cancer requires further investigation.
Proceedings of the 49th Annual ASTRO Meeting
Site of second malignancy Brain
Lung/Mediastinum
Breast Colon Duodenum Stomach Prostate Bladder Uterus Sino-nasal/Nasopharynx Soft tissue
Bone Skin Lymphoma Leukemia
S179
Observed Incidence
Histology
4 2 1 5 1 1 3 2 1 1 1 3 1 1 2 1 1 1 1 6 1 5 2
Glioblastoma multiforme Schwannoma Meningioma Non-small cell carcinoma Small cell carcinoma Teratoma Adenocarcinoma Adenocarcinoma Adenoid cystic carcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Transitional cell carcinoma Adenocarcinoma Squamous cell carcinoma Liposarcoma (retroperitoneal) Desmoid (chest wall) Malignant fibrous histiocytoma (sacrum) Squamous cell carcinoma (temporal bone) Squamous cell carcinoma Malignant melanoma Lymphoma Leukemia
Author Disclosure: C.S. Chung, None; T. Yock, None; J. Johnson, None; B. Esty, None; N. Tarbell, None.
1076
Adverse Impact of Mucositis on Health Related Quality of Life Outcomes and Resource use in Head and Neck Cancer Patients Receiving Radiation
A. S. Garden1, R. B. Tishler2, A. Barasch3, M. T. Brennan4, P. M. Harari5, M. R. Kudrimoti6, C. J. Schultz7, D. G. Brachman8, M. Vera-Llonch9, D. Keefe10 1 M.D. Anderson Cancer Center, Houston, TX, 2Dana Farber Cancer Institute, Boston, MA, 3The University of Alabama at Birmingham, Birmingham, AL, 4Carolinas Medical Center, Charlotte, NC, 5University of Wisconsin Cancer Center, Madison, WI, 6University of Kentucky, Lexington, KY, 7Medical College of Wisconsin, Milwaukee, WI, 8St. Josephs Hospital, Phoenix, AZ, 9 Policy Analysis, Inc., Brookline, MA, 10Royal Adelaide Hospital, North Terrace, SA, Australia
Background: The negative impact of oral mucositis (OM) caused by radiation therapy (RT) for head and neck cancers (HNC) on health, economic and quality of life (QoL) outcomes has been reported in retrospective studies, but it is likely that these underestimate OM’s true influence on resource use and QoL. We report interim results of a prospective observational study to estimate OM’s impact more accurately. Materials/Methods: Patients (pts) with oral cavity, oropharynx, hypopharynx (H), or larynx (L) cancers were enrolled prior to RT at 44 international centers. At baseline and daily thereafter, pts completed the OMDQ, a validated questionnaire that measures mouth and throat soreness (MTS), and overall health (OH). Pts scored MTS on a scale of 0 (‘‘none’’) to 4 (‘‘extreme’’) soreness and OH, from 0 (‘‘worst possible’’) to 10 (‘‘perfect’’) health. Pts completed the FACT-E, a validated QoL instrument, weekly, including its functional wellbeing (FWB) subscale. To describe resource use, pts were categorized by peak MTS score during RT. The relationships between paired, same day self-reports of MTS and OH, FACT-E, or FWB scores were described as means; standard errors were corrected for within-pt correlation using random effects linear regression. Mean scores were adjusted for baseline ECOG performance status (PS), chemotherapy (ctx) use, and cancer site. Results: 94 of a planned 270 pts have completed RT. 72% were males, 95% had good ECOG (0 or 1) PS status at baseline, and their mean age was 55 yrs. 25 (27%) pts had L or HP cancers, 67 (71%) received IMRT, and 56 (60%) received ctx. 100% of pts reported MTS at some time during RT; in 85%, the peak MTS was rated 3 or 4. 28% (95% CI: 18%–39%) of pts with peak MTS scores of 3– 4 required non-prophylactic gastrostomy tube insertion compared with 7% (95% CI: 0%–34%) of pts with peak MTS scores of 0–2. Similar findings (in pts with high and low MTS scores, respectively) were observed for hospitalization, 19% (95% CI: 11%–29%) vs 14% (95% CI: 2%–43%), and for Emergency Room (ER) visits, 15% (95% CI: 8%–25%) vs 7% (95% CI: 0%–34%). Pts reported high OH, QoL, and FWB when little or no MTS was present. But OH, QoL, and FWB decreased as MTS increased (See table). Conclusions: All pts with HNC report MTS during RT. Pts who report the highest peak MTS scores use more costly resources (ER and hospital visits, gastrostomy tubes) and report poorer OH, QoL, and FWB than previously described. These findings illustrate the need for interventions to prevent OM. Relationship between MTS and 726 paired, same-day reports of OH, QoL, and FWB in 94 pts.