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M.C. Pietanza



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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-017 - Factors Influencing Utilization of Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer (ID 1915)

      09:30 - 09:30  |  Author(s): M.C. Pietanza

      • Abstract

      Background
      Prophylactic cranial irradiation (PCI) improves survival in limited-stage small cell lung cancer (LS-SCLC). However, PCI is not always delivered to these patients, possibly due to concerns about neurocognitive effects. Efforts to reduce neurotoxicity of PCI, such as hippocampal-sparing radiation, may mitigate these concerns. Little is known about the utilization rate of PCI and the reasons it is not delivered. Therefore, we reviewed the experience with LS-SCLC at a large academic institution to determine the rate of PCI use and factors associated with the lack of use.

      Methods
      We retrospectively reviewed all patients with LS-SCLC treated at our institution between 2000 and 2012. Receipt of PCI was recorded, as well as information about clinical presentation and initial treatment. In patients who did not receive PCI, we reviewed clinical notes from both medical and radiation oncologists to determine the reason. Overall survival (OS) and brain metastasis-free survival (BMFS) were estimated using the Kaplan-Meier technique. Pearson’s chi-squared test was used to evaluate factors associated with PCI use.

      Results
      We identified 229 patients treated with thoracic radiotherapy (TRT) for LS-SCLC at our institution. Median followup was 15.1 months. Of these, 119 (52.0%) did not receive PCI. Thirty-three patients (27.7%) had progressive disease or concern for progression after initial therapy and therefore did not receive PCI. The next most common causes for no PCI were patient refusal (n=25, 21%) or deemed medically unfit by an oncologist (n=25, 21%). In 20 patients (16.8%), the reason for lack of PCI could not be ascertained. Other infrequent causes were patient death or lack of followup (n=8), age (n=3), and prior radiotherapy to the head (n=2). Patients who did not get PCI were significantly older (p<0.001) and had worse performance status at initial presentation (p<0.001). Patients who received sequential rather than concurrent chemoradiation, or who received once-daily rather than twice-daily TRT, were also significantly less likely to receive PCI (p<0.001). Patients who did not receive PCI had significantly worse OS (median 17 vs. 30 months, p=0.01) and BMFS (71% vs. 91% at 1 year, p=0.02) than those who did.

      Conclusion
      Even at a major academic center, fewer than half of patients with LS-SCLC ultimately receive PCI. Patients receiving PCI had better intracranial control. They also had better OS, but this is likely also attributable to other clinical and treatment characteristics. Younger and fitter patients, as well as those receiving optimal TRT, are significantly more likely to undergo PCI. The most common reason for lack of PCI is progression of disease after initial therapy, which is clinically appropriate. However, a significant number of patients are appropriate for PCI yet refuse therapy, generally due to concerns about toxicity. PCI is withheld from an equivalent number of patients due to oncologist concerns about ability to tolerate therapy. This indicates that efforts to reduce neurotoxicity of PCI, such as hippocampal-sparing radiation, may impact a significant number of patients with LS-SCLC and expand the application of this survival-enhancing intervention.

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    P3.13 - Poster Session 3 - SCLC (ID 202)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.13-007 - Pilot trial of an adjuvant pentavalent vaccine for patients with small cell lung cancer (SCLC) (ID 2830)

      09:30 - 09:30  |  Author(s): M.C. Pietanza

      • Abstract

      Background
      Despite initial responses to chemotherapy, SCLC typically progresses within a few months. Targeting residual disease has the potential to improve outcomes. A number of tumor specific glycolipid antigens have been identified and are potential targets for immune therapies. In a series of phase I clinical trials, vaccination with each of these antigens individually was safe and induced antibody responses in the majority of patients. Preclinical data indicate that combining these antigens will expand the immunogenicity across a broader array of SCLC tumor cells. We conducted this pilot trial to determine the safety and immunogenicity of a vaccine combining five of these antigens.

      Methods
      Patients with limited or extensive stage SCLC who have completed initial chemotherapy +/- thoracic or cranial irradiation with a maintained response are eligible. Vaccinations must start within 3-8 weeks of the last chemotherapy, and at least 1 week after radiation. Patients receive KLH-conjugates of GD2L, GD3L, Globo H, fucosyl GM1, and N-propionylated polysialic acid (30mcg each) plus OPT-821 adjuvant (150mcg) subcutaneously on weeks 1, 2, 3, 9, 20, and 32. One cycle of etoposide/platinum chemotherapy was administered in week 6. A significant immune response is defined as an antibody titer of ≥ 1:80 by ELISA against a given antigen or a ≥ 8 fold increase over baseline for patients with a detectable baseline titer. The vaccine would be deemed worthy of further study if >5 patients had an immune response to 3 or more antigens.

      Results
      Ten patients were treated, including 9 with extensive stage, 4 women, 7 with prior brain radiation. The number of vaccinations administered was: 1 (1pt), 3 (2), 4 (3), 5 (2), and 6 (2). Toxicity was limited to mild skin reactions. One patient was taken off study after he developed aphasia the day after the first vaccination; MRI brain was unremarkable and symptoms resolved spontaneously. No patients met the predefined criteria for immune response. Six patients had increases in IgM titers to 1-2 antigens. The median time to progression was 4 months. The two patients with the strongest IgM responses to Globo H and fucosyl GM1, and also the only IgG responses to fucosyl GM1, had progression of disease 7 and 9 months after starting the vaccines, and both progressed initially in the brain only.

      Conclusion
      The polyvalent vaccine is safe, but fewer patients than expected had a significant immune response, Two patients with immune responses experienced a longer than expected time to progression. A second cohort of patients is now receiving the vaccinations over a shorter period of time and without the added cycle of chemotherapy. Five out of 10 of those patients have been enrolled, and preliminary data will be available on those patients for the meeting. Following completion of this pilot trial, a multicenter randomized trial is planned. Supported by MabVax Therapeutics’s NIH grant R41 CA128363 and a grant from FAMRI.