Comorbidity is an independent factor influencing patient selection for combined modality therapy for treatment of stage III non-small cell lung cancer (NSCLC)

Abstract

Purpose/ObjectiveTo determine the influence of comorbidity in patient selection for treatment of stage III NSCLC with combined modality therapy (CMT) using chemotherapy and radiotherapy.Materials/MethodsOne hundred and two patients with a Karnofsky Performance Score (KPS) of 70 or above, and clinical stage III NSCLC (AJCC 1997) diagnosed between January 1994, and July 2002 were analyzed retrospectively for comorbidity. Fifty-eight patients (57%) were treated at the Zablocki Veterans Administration Hospital (VAH) and 44 patients (43%) at a Medical College of Wisconsin affiliated community hospital (MCWAH). All patients were initially evaluated with a computerized tomography (CT) of the chest and upper abdomen. CT or Magnetic Resonance Imaging of the head and bone scan were performed in 81% (83) and 84% (86) of the patients, respectively. All patients received radiotherapy, and 57 (56%) received CMT. The primary tumor and involved lymph nodes were treated to a median dose of 63Gy (Range: 16- 83.8Gy) with a median daily fraction of 180cGy (Range: 180–215cGy). Four patients received hyperfractionated radiotherapy using 1.2Gy fractions twice daily, and one patient, 1.1Gy three times a day. Eight patients could not complete radiotherapy secondary to worsening of their medical condition or patient refusal. Of the patients receiving sequential and/or concurrent chemotherapy, carboplatin and taxol were used in 37, cisplatin and VP-16 or vinblastine in 16, gemcitabine with taxol or carboplatin in 3, and taxol only in 1 patient. Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). The CIRS-G comprehensively grades comorbidity in 14 different organ systems. Each organ system is assigned a grade from 0 (no problem) through 4 (extremely severe impairment) according to absence or presence and severity of any comorbidity related to the corresponding system. Hospital charts were reviewed for history and physical examination, past medical and surgical history, social history, medications, complete blood counts, liver and kidney functions, and serum biochemistry tests to assess the CIRS-G score. Effects of presence of an extremely severe (score of 4) score, was tested for impact on patient selection and survival.ResultsMedian age was 66 (40–85). Thirty-four (33%) patients had >5% weight loss within 6 months prior to diagnosis and 31 (30%) had an extremely severe comorbidity per the CIRS-G scale. Median survival was 10.03 months (8.1–11.9). One, 2 and 5 year overall survivals (OS) were 42.2%, 26.9% and 12.8% respectively. Univariate and multivariate analysis revealed that presence of a CIRS-G score of 4 (extremely severe comorbidity) (p = 0.02) and use of radiation only (p < 0.01) were associated with a statistically significant inferior OS, whereas age ≥70, clinical stage IIIB, >5% weight loss, and radiation dose >63Gy did not have any statistically significant influence on OS. Patients receiving CMT were significantly younger (p < 0.001), with less comorbidity (p < 0.001) and weight loss (p = 0.003) compared to patients receiving radiotherapy alone. A multivariate analysis revealed that comorbidity (p = 0.007), weight loss (0.002) and age (p < 0.001) were independent factors influencing patient selection for CMT, whereas stage and hospital where patients were treated were not. The statistically higher (p = 0.001) incidence of severe comorbidity in the VAH patients compared to the MCWAH patients was likely the major reason for the less frequent use of chemotherapy in VAH patients (p = 0.001).ConclusionsThe importance of comorbidity cannot be ignored in treatment of stage III NSCLC. Comorbidity is not only an independent prognostic factor influencing OS, but it also effects patient selection for CMT independent of age and weight loss in patients with KPS ≥70. Therefore, comorbidity assessment should be included in protocols studying advanced stage NSCLC and may be useful for stratification Purpose/ObjectiveTo determine the influence of comorbidity in patient selection for treatment of stage III NSCLC with combined modality therapy (CMT) using chemotherapy and radiotherapy. To determine the influence of comorbidity in patient selection for treatment of stage III NSCLC with combined modality therapy (CMT) using chemotherapy and radiotherapy. Materials/MethodsOne hundred and two patients with a Karnofsky Performance Score (KPS) of 70 or above, and clinical stage III NSCLC (AJCC 1997) diagnosed between January 1994, and July 2002 were analyzed retrospectively for comorbidity. Fifty-eight patients (57%) were treated at the Zablocki Veterans Administration Hospital (VAH) and 44 patients (43%) at a Medical College of Wisconsin affiliated community hospital (MCWAH). All patients were initially evaluated with a computerized tomography (CT) of the chest and upper abdomen. CT or Magnetic Resonance Imaging of the head and bone scan were performed in 81% (83) and 84% (86) of the patients, respectively. All patients received radiotherapy, and 57 (56%) received CMT. The primary tumor and involved lymph nodes were treated to a median dose of 63Gy (Range: 16- 83.8Gy) with a median daily fraction of 180cGy (Range: 180–215cGy). Four patients received hyperfractionated radiotherapy using 1.2Gy fractions twice daily, and one patient, 1.1Gy three times a day. Eight patients could not complete radiotherapy secondary to worsening of their medical condition or patient refusal. Of the patients receiving sequential and/or concurrent chemotherapy, carboplatin and taxol were used in 37, cisplatin and VP-16 or vinblastine in 16, gemcitabine with taxol or carboplatin in 3, and taxol only in 1 patient. Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). The CIRS-G comprehensively grades comorbidity in 14 different organ systems. Each organ system is assigned a grade from 0 (no problem) through 4 (extremely severe impairment) according to absence or presence and severity of any comorbidity related to the corresponding system. Hospital charts were reviewed for history and physical examination, past medical and surgical history, social history, medications, complete blood counts, liver and kidney functions, and serum biochemistry tests to assess the CIRS-G score. Effects of presence of an extremely severe (score of 4) score, was tested for impact on patient selection and survival. One hundred and two patients with a Karnofsky Performance Score (KPS) of 70 or above, and clinical stage III NSCLC (AJCC 1997) diagnosed between January 1994, and July 2002 were analyzed retrospectively for comorbidity. Fifty-eight patients (57%) were treated at the Zablocki Veterans Administration Hospital (VAH) and 44 patients (43%) at a Medical College of Wisconsin affiliated community hospital (MCWAH). All patients were initially evaluated with a computerized tomography (CT) of the chest and upper abdomen. CT or Magnetic Resonance Imaging of the head and bone scan were performed in 81% (83) and 84% (86) of the patients, respectively. All patients received radiotherapy, and 57 (56%) received CMT. The primary tumor and involved lymph nodes were treated to a median dose of 63Gy (Range: 16- 83.8Gy) with a median daily fraction of 180cGy (Range: 180–215cGy). Four patients received hyperfractionated radiotherapy using 1.2Gy fractions twice daily, and one patient, 1.1Gy three times a day. Eight patients could not complete radiotherapy secondary to worsening of their medical condition or patient refusal. Of the patients receiving sequential and/or concurrent chemotherapy, carboplatin and taxol were used in 37, cisplatin and VP-16 or vinblastine in 16, gemcitabine with taxol or carboplatin in 3, and taxol only in 1 patient. Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). The CIRS-G comprehensively grades comorbidity in 14 different organ systems. Each organ system is assigned a grade from 0 (no problem) through 4 (extremely severe impairment) according to absence or presence and severity of any comorbidity related to the corresponding system. Hospital charts were reviewed for history and physical examination, past medical and surgical history, social history, medications, complete blood counts, liver and kidney functions, and serum biochemistry tests to assess the CIRS-G score. Effects of presence of an extremely severe (score of 4) score, was tested for impact on patient selection and survival. ResultsMedian age was 66 (40–85). Thirty-four (33%) patients had >5% weight loss within 6 months prior to diagnosis and 31 (30%) had an extremely severe comorbidity per the CIRS-G scale. Median survival was 10.03 months (8.1–11.9). One, 2 and 5 year overall survivals (OS) were 42.2%, 26.9% and 12.8% respectively. Univariate and multivariate analysis revealed that presence of a CIRS-G score of 4 (extremely severe comorbidity) (p = 0.02) and use of radiation only (p < 0.01) were associated with a statistically significant inferior OS, whereas age ≥70, clinical stage IIIB, >5% weight loss, and radiation dose >63Gy did not have any statistically significant influence on OS. Patients receiving CMT were significantly younger (p < 0.001), with less comorbidity (p < 0.001) and weight loss (p = 0.003) compared to patients receiving radiotherapy alone. A multivariate analysis revealed that comorbidity (p = 0.007), weight loss (0.002) and age (p < 0.001) were independent factors influencing patient selection for CMT, whereas stage and hospital where patients were treated were not. The statistically higher (p = 0.001) incidence of severe comorbidity in the VAH patients compared to the MCWAH patients was likely the major reason for the less frequent use of chemotherapy in VAH patients (p = 0.001). Median age was 66 (40–85). Thirty-four (33%) patients had >5% weight loss within 6 months prior to diagnosis and 31 (30%) had an extremely severe comorbidity per the CIRS-G scale. Median survival was 10.03 months (8.1–11.9). One, 2 and 5 year overall survivals (OS) were 42.2%, 26.9% and 12.8% respectively. Univariate and multivariate analysis revealed that presence of a CIRS-G score of 4 (extremely severe comorbidity) (p = 0.02) and use of radiation only (p < 0.01) were associated with a statistically significant inferior OS, whereas age ≥70, clinical stage IIIB, >5% weight loss, and radiation dose >63Gy did not have any statistically significant influence on OS. Patients receiving CMT were significantly younger (p < 0.001), with less comorbidity (p < 0.001) and weight loss (p = 0.003) compared to patients receiving radiotherapy alone. A multivariate analysis revealed that comorbidity (p = 0.007), weight loss (0.002) and age (p < 0.001) were independent factors influencing patient selection for CMT, whereas stage and hospital where patients were treated were not. The statistically higher (p = 0.001) incidence of severe comorbidity in the VAH patients compared to the MCWAH patients was likely the major reason for the less frequent use of chemotherapy in VAH patients (p = 0.001). ConclusionsThe importance of comorbidity cannot be ignored in treatment of stage III NSCLC. Comorbidity is not only an independent prognostic factor influencing OS, but it also effects patient selection for CMT independent of age and weight loss in patients with KPS ≥70. Therefore, comorbidity assessment should be included in protocols studying advanced stage NSCLC and may be useful for stratification The importance of comorbidity cannot be ignored in treatment of stage III NSCLC. Comorbidity is not only an independent prognostic factor influencing OS, but it also effects patient selection for CMT independent of age and weight loss in patients with KPS ≥70. Therefore, comorbidity assessment should be included in protocols studying advanced stage NSCLC and may be useful for stratification