Atezolizumab for Advanced Alveolar Soft Part Sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported. METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action. RESULTS: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1. CONCLUSIONS: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.).

A randomized, open-label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft-tissue sarcoma.

BACKGROUND: Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. METHODS: The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). RESULTS: A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). CONCLUSIONS: The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.

Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma.

The average survival time for patients with recurrent glioblastoma is between 5 and 9 months. Phase I and II trials have shown a modest survival benefit with combination temozolomide and other chemotherapeutics. We conducted a phase I trial of dose-escalating temozolomide with bevacizumab and the proteasome inhibitor bortezomib for patients with recurrent disease. Three groups of three patients were scheduled to receive daily doses of temozolomide at 25, 50, and 75 mg/m2. Fixed doses of bortezomib and bevacizumab were given at standard intervals. Patients were monitored for dose-limiting toxicities (DLT) to determine the maximum-tolerated dose (MTD) of temozolomide with this regimen. No DLT were seen in the first two groups (25 and 50 mg/m2 temozolomide). One patient in the 75 mg/m2 group experienced a grade 4 elevation of ALT and three more patients were accrued for a total of six patients at that dose level. No other DLT occurred, thus making 75 mg/m2 the MTD. Progression-free survival was 3.27 months for all patients and mean overall survival was 20.75 months. The MTD of temozolomide was 75 mg/m2 in combination with bevacizumab and bortezomib for recurrent glioblastoma. Only one patient experienced a severe (Grade 4) elevation of ALT. This study will provide the framework for further studies to elicit effectiveness and better determine a safety profile for this drug combination.

Rare Delayed Ifosfamide Encephalopathy: A Case Report of Chemotherapeutic Neurotoxicity.

Introduction: Neurotoxicity is a well-documented side effect of ifosfamide chemotherapy. The presentation includes hallucinations, seizures, disorientation, coma, and death. Treatment with methylene blue can shorten the duration and severity of symptoms. Ifosfamide neurotoxicity almost always happens during or shortly after drug infusion and so is usually immediately recognized. Here, we describe a case of ifosfamide neurotoxicity with onset 14 days after treatment started. Case Presentation: A 25-year-old woman with round cell sarcoma of the jaw presented to the emergency department with 2 days of encephalopathy and bizarre behavior. Antipsychotic medications and benzodiazepines produced no benefit. After consultation, oncology recommended methylene blue, hypothesizing that her symptoms could be a rare presentation of delayed ifosfamide-induced neurotoxicity, 14 days after first administration. After 4 days of methylene blue infusion, her functioning returned to baseline. Conclusion: Delayed ifosfamide-related neurotoxicity is a rare side effect of this chemotherapeutic agent and should be considered in the workup of altered mental status, even if symptoms occur after the previously accepted 5-day standard. In such patients, delayed symptomology may require extended use of methylene blue as treatment.

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery.

BACKGROUND: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. METHODS: We conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response. RESULTS: A total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. CONCLUSIONS: A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms. CLINICALTRIALS: gov identifier: NCT01141491.

A unique case of an indolent CD56-positive T-cell lymphoproliferative disorder of the gastrointestinal tract: a lesion potentially misdiagnosed as natural killer/T-cell lymphoma.

Primary intestinal natural killer (NK)/T-cell lymphoma (nasal-type) and enteropathy-associated T-cell lymphoma, type II, are CD56-positive lymphoproliferative disorders with very poor survival rates. We report a long-surviving patient with a CD56-positive T-cell lymphoproliferative disorder of the gastrointestinal tract that presented as vomiting, diarrhea, weight loss, and pain. This patient was referred to the university hospital as a case of peripheral T-cell lymphoma due to this CD56-positive lymphocyte population. There was no evidence of enteropathy; and the infiltrates were negative for CD8, Epstein-Barr virus, and T-cell receptor gene rearrangement. Despite its persistence for 8 years, the clinical course has remained indolent. This report confirms that patients may rarely present with a CD56-positive NK/T-cell-like proliferation of the gastrointestinal tract, yet follow an indolent clinical course. Thus, all pathologic features of enteropathy-associated T-cell lymphoma or NK/T-cell lymphoma should be present before making this diagnosis and exposing the patient to toxic chemotherapy.

A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors.

PURPOSE: To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN: MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation proceeded by 100% per toxicity criteria. Intra-patient dose escalation was permitted. RESULTS: Twenty patients received a total of 151 infusions of MN-029. No DLTs or grade 4 toxicities occurred. The most common adverse events were nausea, vomiting, arthralgias, and headache. One patient developed acute substernal chest pain 4 days after his first dose of MN-029 and was removed from the study. An MTD was not determined. The recommended phase II dose was identified as 180 mg/m(2)/week. One patient with advanced pancreatic cancer attained a partial response lasting 10 weeks. CONCLUSIONS: MN-029 was well tolerated in this schedule. Further development of this class of agents is warranted, especially in combination with other anti-cancer treatments.

Pulmonary langerhans cell histiocytosis diagnosed in a cervical lymph node: a case report.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is usually confined to the lungs and is therefore an unexpected finding in a cervical lymph node. CASE: A 52-year-old male with a 40-pack-year smoking history presented to our clinic with cough, fever and cervical lymphadenopathy. Chest computed tomography (CT) showed bilateral pulmonary nodules and enlarged mediastinal lymph nodes, worrisome for an infectious or malignant process. Bronchioloalveolar lavage was nondiagnostic. Fine needle aspiration cytology of the enlarged cervical lymph node revealed atypical histiocytoid cells, suspicious for malignancy. Immunohistochemistry revealed CD1a- and S-100-positive Langerhans cells. These findings, along with the patient's extensive smoking history and characteristic radiographic nodules, favored a diagnosis of PLCH with cervical lymph node involvement. The patient was advised to cease smoking, and no therapy was administered. Months later, follow-up chest CT showed spontaneous resolution of the lung nodules. CONCLUSION: The demonstration of Langerhans cells by immunohistochemical staining of CD1a and S-100 on a fine needle aspiration cell block is a useful diagnostic adjunct. In this case, definitive cytology for Langerhans cells in the appropriate clinical and radiologic setting allowed us to arrive at the correct diagnosis of PLCH in a minimally invasive manner.

Dose-response assessment by quantitative MRI in a phase 1 clinical study of the anti-cancer vascular disrupting agent crolibulin.

The vascular disrupting agent crolibulin binds to the colchicine binding site and produces anti-vascular and apoptotic effects. In a multisite phase 1 clinical study of crolibulin (NCT00423410), we measured treatment-induced changes in tumor perfusion and water diffusivity (ADC) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI), and computed correlates of crolibulin pharmacokinetics. 11 subjects with advanced solid tumors were imaged by MRI at baseline and 2-3 days post-crolibulin (13-24 mg/m2). ADC maps were computed from DW-MRI. Pre-contrast T1 maps were computed, co-registered with the DCE-MRI series, and maps of area-under-the-gadolinium-concentration-curve-at-90 s (AUC90s) and the Extended Tofts Model parameters ktrans, ve, and vp were calculated. There was a strong correlation between higher plasma drug [Formula: see text] and a linear combination of (1) reduction in tumor fraction with [Formula: see text] mM s, and, (2) increase in tumor fraction with [Formula: see text]. A higher plasma drug AUC was correlated with a linear combination of (1) increase in tumor fraction with [Formula: see text], and, (2) increase in tumor fraction with [Formula: see text]. These findings are suggestive of cell swelling and decreased tumor perfusion 2-3 days post-treatment with crolibulin. The multivariable linear regression models reported here can inform crolibulin dosing in future clinical studies of crolibulin combined with cytotoxic or immune-oncology agents.

Recurrent Epithelioid Hemangioma of the Bony Pelvis Responding to Propranolol.

Epithelioid hemangioma is an uncommon benign vascular neoplasm which can arise in bone. Resection is generally curative, but occasionally lesions recur and recurrence after surgery can be morbid and destructive. Recent case reports have described the effective use of oral propranolol to control recurrent epithelioid hemangioma of the orbit. We report the case of a 26 year old man with recurrent aggressive osseous epithelioid hemangioma in the pelvis of which has been controlled for over a year with outpatient propranolol monotherapy.

The use of a predictive statistical model to make a virtual control arm for a clinical trial.

BACKGROUND: Randomized clinical trials compare participants receiving an experimental intervention to participants receiving standard of care (SOC). If one could predict the outcome for participants receiving SOC, a trial could be designed where all participants received the experimental intervention, with the observed outcome of the experimental group compared to the prediction for those individuals. METHODS: We used the CancerMath calculator to predict outcomes for participants in two large clinical trials of adjuvant chemotherapy for breast cancer: NSABPB15 and CALGB9344. NSABPB15 was the training set, and we used the modified algorithm to predict outcomes for two groups from CALGB9344: one which received standard of care (SOC) chemotherapy and one which received paclitaxel in addition. We made a prediction for each individual CALGB9344 participant, assuming each received only SOC. RESULTS: The predicted outcome for the group which received only SOC matched what was observed in the CALGB9344 trial. In contrast, the predicted outcome for the group also receiving paclitaxel was significantly worse than what was observed for this group. This matches the conclusion of CALGB9344 that adding paclitaxel to SOC improves survival. CONCLUSION: This project proves that a statistical model can predict the outcome of clinical trial participants treated with SOC. In some circumstances, a predictive model could be used instead of a control arm, allowing all participants to receive experimental treatment. Predictive models for cancer and other diseases could be constructed using the vast amount of outcomes data available to the federal government, and made available for public use.

Response assessment of meningioma: 1D, 2D, and volumetric criteria for treatment response and tumor progression.

BACKGROUND: Meningiomas are the most common primary brain tumors in adults. Due to their variable growth rates and irregular tumor shapes, response assessment in clinical trials remains challenging and no standard criteria have been defined. We evaluated 1D, 2D, and volume imaging criteria to assess whether a volumetric approach might be a superior surrogate for overall survival (OS). METHODS: In this retrospective multicenter study, we evaluated the clinical and imaging data of 93 patients with recurrent meningiomas treated with pharmacotherapy. One-dimensional (1D), 2D, and volumetric measurements of enhancing tumor on pre- and post-treatment MRI were compared at 6 and 12 months after treatment initiation. Cox proportional hazards models were used to examine the relationship between each imaging criterion and OS. RESULTS: The median age of the patient cohort is 51 years (range 12-88), with 14 World Health Organization (WHO) grade I, 53 WHO grade II, and 26 WHO grade III meningiomas. Volumetric increase of 40% and unidimensional increase by 10 mm at 6 months and 12 months provided the strongest association with overall survival (HR = 2.58 and 3.24 respectively, p<0.01). Setting a volume change threshold above 40% did not correlate with survival. The interobserver agreement of 1D, 2D, and volume criteria is only moderate (kappa = 0.49, 0.46, 0.52, respectively). None of the criteria based on tumor size reduction were associated with OS (P > 0.09). CONCLUSION: Compared with 1D (Response Evaluation Criteria In Solid Tumors 1.1) and 2D (Response Assessment in Neuro-Oncology) approaches, volumetric criteria for tumor progression has a stronger association with OS, although the differences were only modest. The interobserver variability is moderate for all 3 methods. Further validation of these findings in an independent patient cohort is needed.

A phase I study of bexarotene and rosiglitazone in patients with refractory cancers.

BACKGROUND: Preclinical studies have shown that binding of PPAR-gamma (polysome-proliferator activated receptor gamma) and retinoid-X receptor (RXR) to their ligands can slow growth and promote differentiation of malignant cells. Rosiglitazone, a PPAR-gamma ligand, is approved for treatment of insulin-resistant diabetes, and bexarotene, a RXR ligand, is approved for treatment of cutaneous T-cell lymphoma. After binding to its ligand, the PPAR-gamma receptor heterodimerizes with the RXR resulting in synergistic effects in preclinical models. We conducted a phase I study of bexarotene and rosiglitazone to define the MTD of rosiglitazone in this combination regimen. METHODS: Patients with resistant solid tumors received bexarotene 300 mg/m(2)/day. The starting dose of rosiglitazone was 4 mg/day and was escalated in five cohorts by 2-mg increments up to 12 mg/day. Both drugs were continued until disease progression or toxicity was observed. Patients received atorvastatin 10 mg/day to control bexarotene-related hypertriglyceridemia. RESULTS: Twenty-three patients were enrolled, with a median of 4 prior regimens (range 0-8). The study was closed after completing the 12 mg/day cohort without encountering dose-limiting toxicity. The most common grade 3 or 4 toxicities were hypertriglyceridemia (17%), dyspnea (9%), nausea (9%), and dehydration (9%). No objective responses were observed. CONCLUSIONS: The combination of bexarotene (300 mg/m(2)/day) and rosiglitazone (12 mg/day) is safe and feasible but did not result in objective responses in heavily pretreated patients with solid tumors. This combination is suitable for evaluation in other conditions such as hematologic malignancies and inflammatory diseases.

Recurrent Meningioma of the Cervical Spine, Successfully Treated with Liposomal Doxorubicin.

There is no standard systemic treatment for persons with recurrent meningioma who have exhausted surgery and radiation options. Liposomal doxorubicin is a cytotoxic chemotherapy which is sustainable and tolerable, with activity against a range of solid tumors. There exists one reported case of metastatic meningioma effectively treated with liposomal doxorubicin. We report a second case. Our patient, a 35-year-old man with recurrent meningioma compressing the cervical spinal cord received liposomal doxorubicin for 22 months with clinical improvement, minimal toxicity, and slow regression of his tumor. He is well and without progression 18 months after stopping chemotherapy and 4 years after his last progression event.

Norethindrone substituted for megestrol in the treatment of metastatic endometrial carcinoma: Three cases.

•Progestins can produce clinical benefit in a subset of women with metastatic endometrial cancer.•Corticosteroid-related effects of megestrol can cause morbidity over the long term.•Norethindrone is a progestin without corticosteroid side effects.•A switch from megestrol to norethindrone decreased toxicity with continued benefit.•A clinical trial of norethindrone for this population of patients would be welcome.

Timed sequential therapy of the selective T-type calcium channel blocker mibefradil and temozolomide in patients with recurrent high-grade gliomas.

Background: Mibefradil (MIB), previously approved for treatment of hypertension, is a selective T-type calcium channel blocker with preclinical activity in high-grade gliomas (HGGs). To exploit its presumed mechanism of impacting cell cycle activity (G1 arrest), we designed a phase I study to determine safety and the maximum tolerated dose (MTD) of MIB when given sequentially with temozolomide (TMZ) in recurrent (r)HGG. Methods: Adult patients with rHGG ≥3 months from TMZ for initial therapy received MIB in 4 daily doses (q.i.d.) for 7 days followed by standard TMZ at 150-200 mg/m2 for 5 days per 28-day cycle. MIB dose escalation followed a modified 3 + 3 design, with an extension cohort of 10 patients at MTD who underwent 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET imaging, to image proliferation before and after 7 days of MIB. Results: Twenty-seven patients were enrolled (20 World Health Organization grade IV, 7 grade III; median age 50 y; median KPS 90). The MTD of MIB was 87.5 mg p.o. q.i.d. Dose-limiting toxicities were elevation of alanine aminotransferase/aspartate aminotransferase (grade 3) and sinus bradycardia. The steady-state maximum plasma concentration of MIB at the MTD was 1693 ± 287 ng/mL (mean ± SD). 18F-FLT PET imaging showed a significant decline in standardized uptake value (SUV) signal in 2 of 10 patients after 7 days of treatment with MIB. Conclusions: MIB followed by TMZ was well tolerated in rHGG patients at the MTD. The lack of toxicity and presence of some responses in this selected patient population suggest that this regimen warrants further investigation.

Metastatic Angiosarcoma with Kasabach-Merritt Syndrome Responsive to Gemcitabine and Vinorelbine after Failure of Liposomal Doxorubicin and Paclitaxel: A Case Report.

Kasabach-Merritt syndrome (KMS) describes a consumptive coagulopathy associated with certain vascular tumors. It is thought that platelets are destroyed as they circulate through the aberrant endothelial surfaces associated with these tumors. Most published literature describes infants with kaposiform hemangioendothelioma, but a similar syndrome can complicate angiosarcoma in adults. This report describes a man with metastatic angiosarcoma arising in the scalp in whom disease progression was complicated by profound thrombocytopenia consistent with KMS. His disease and associated KMS had progressed previously through paclitaxel and then through liposomal doxorubicin. It did not respond to paclitaxel and bevacizumab, but responded almost completely to chemotherapy with gemcitabine and vinorelbine. Six months later, progression through ongoing chemotherapy then responded to chemotherapy with cyclophosphamide and sirolimus.

Metastatic Alveolar Soft Part Sarcoma Responsive to Pazopanib after Progression through Sunitinib and Bevacizumab: Two Cases.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with a propensity for lung metastases and indolent progression. ASPS is not responsive to chemotherapy, but there are case reports and small series describing benefit from drugs targeting the VEGF pathway. These drugs include sunitinib, cediranib and bevacizumab. There is no established second-line treatment for persons with ASPS progressing through first-line targeted therapy. We report two individuals with metastatic ASPS who obtained disease stabilization from sunitinib lasting over a year. After subsequent progression through sunitinib and second-line bevacizumab, both individuals again had disease response and subsequent stabilization from pazopanib.

Differential prognostic impact of comorbidity.

PURPOSE: Cancer patients with concurrent comorbid conditions have worse outcomes than patients with no comorbidities. We hypothesized that the prognostic impact of comorbidities would be greatest for patients with cancers associated with a long natural history and least in patients with aggressive cancers. PATIENTS AND METHODS: Using the Barnes-Jewish Hospital Oncology Data Services cancer registry, we grouped 11,558 patients with breast, lung, colon, or prostate cancer by morphologic stage at diagnosis and then determined the 1-year overall survival rate for each group. Overall, severity of comorbidity was assessed from chart review and classified into one of four groups: none, mild, moderate, or severe. The relative prognostic impact of comorbidity was measured by the hazard ratio and adjusted for the prognostic impact of age, race, and sex. RESULTS: One-year overall survival rate ranged from 20% for 1,005 patients with distant spread of lung cancer to 98% for 3,325 patients with localized prostate cancer. Adjusted hazard ratio of moderate/severe comorbidity (relative to none/mild) ranged from 1.04 to 4.48. The correlation between overall survival rate and severity of comorbidity was statistically significant (r2 = 0.56; P < .001). The proportion of variance in outcome explained by comorbidity ranged from less than 1% to almost 9%, depending on tumor site and stage. CONCLUSION: Concurrent comorbidities had the greatest prognostic impact among groups with the highest survival rate and the least impact in groups with the lowest survival rate. These findings can be used to help determine the role comorbidity information should play in studies of cancer outcomes.