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D. Rice



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    MO14 - Mesothelioma II - Surgery and Multimodality (ID 121)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO14.11 - Safety of hemithoracic pleural intensity-modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM) in the multimodality setting: interim analysis of a phase II study. (ID 2802)

      10:30 - 12:00  |  Author(s): D. Rice

      • Abstract
      • Presentation
      • Slides

      Background
      Pleurectomy/decortication (P/D) is increasingly used for the surgical management of MPM. The presence of the remaining ipsilateral lung poses a challenge when delivering adjuvant radiation therapy, as the risk for radiation pneumonitis (RP) is high. We developed an IMRT technique targeting the entire pleura of the involved hemithorax, with promising early results. Here, we present the interim results of a prospective phase II study to determine the safety and toxicity profile of pleural IMRT following induction chemotherapy and P/D.

      Methods
      Twenty-nine patients with locally advanced MPM have been enrolled to date. All patients received up to four cycles of pemetrexed/platinum chemotherapy. P/D was performed for all resectable patients. Sequential hemithoracic pleural IMRT was then administered with the intent of achieving a total planned dose of 50.4Gy in 28 fractions, as previously described (Rosenzweig et al., IJROBP 2012). All patients were simulated with a 4D-CT scan. A PET scan for image fusion and radiation planning was available for all patients. A Simon two-stage design was applied. A safety analysis after the first 9 patients led to the identification of only one case with ≥grade 3 RP in the first 3 months. The cohort was therefore expanded to 28 evaluable patients, defined as having initiated RT. The primary endpoint is the incidence of ≥grade 3 RP defined per Common Terminology Criteria for Adverse Events, v4.0. Steroids are typically initiated for ≥grade 2 RP.

      Results
      To date, 21 out of 29 patients total are evaluable. The median follow-up is 10 months. The median age at diagnosis is 66 years (range 38-79). Median KPS was 90% (range 70-90%). Three patients had sarcomatoid, 3 had biphasic and 23 had epithelioid MPM. All patients received chemotherapy. Eight patients (28%) had a partial response, nine patients (38%) progressed, and all others had stable disease. Twenty-four patients (83%) underwent surgical exploration. Five patients underwent an extended P/D or P/D, 11 had a partial P/D, and 8 were found to be unresectable. Eight patients were removed from the study prior to receiving IMRT (7 due to disease progression and 1 due to grade 4 pulmonary embolism after one cycle of chemotherapy). To date, nineteen patients have completed IMRT [median dose 4680cGy (range 4500 to 5040cGy)]; one patient had distant disease progression after 16 fractions; one patient is currently on treatment. Five patients experienced grade 2 RP that was successfully controlled with steroids. One patient experienced grade 3 RP requiring supplemental oxygen, but quickly improved after steroid initiation. Other commonly observed ≥grade 2 radiation-related toxicities included fatigue (37%), dyspnea (47%), nausea (42%), esophagitis (26%), and cough (11%). No grade 4 or 5 radiation-related toxicities were observed.

      Conclusion
      Hemithoracic pleural IMRT appears to have an acceptable toxicity profile in this ongoing phase II study. Early intervention with steroids is effective in controlling RP. This novel radiation technique has great promise as a component of lung-sparing multi-modality therapy in locally advanced MPM.

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-010 - Preoperative Flourodeoxyglucose-Positron Emission Tomography Scan with Positive N1 Disease Does Not Predict Worse Survival in Pathologic Stage II Patients (ID 1070)

      09:30 - 16:30  |  Author(s): D. Rice

      • Abstract

      Background
      The rate of fluorodeoxyglucose uptake measured as standardized uptake value (SUV) on positron emission tomography (PET) of the primary tumor has been correlated with tumor aggressiveness and poor survival in patients with lung cancer. A retrospective review of patients with lung cancer who were treated with surgical resection at MD Anderson Cancer Center (MDACC) was performed to determine if the pre-operative SUV uptake of N1 disease has any prognostic significance in patients with pathologic stage II lung cancer.

      Methods
      We reviewed all patients who underwent surgical resection for lung cancer at MDACC from 1998 to 2011. We evaluated non-small cell lung cancer patients who had at least a lobectomy at MDACC as first mode of surgical therapy who had pathologic stage T1-2 and N1 disease and pre-operative PET-CT scan. We determined the clinicopathologic characteristics of patients who had PET-positive N1 disease and compared them to patients who had PET-negative N1 disease. We also performed Kaplan Meier analysis to determine the survival between the two groups.

      Results
      Among patients who underwent surgical resection for lung cancer at MDACC during this time period, 120 patients met the inclusion criteria for the study. There were 100 stage IIA or T1aN1, T1bN1 or T2aN1 and 20 stage IIB or T2bN1 patients in the study. There were 62 patients (50% of the patients) who had a primary tumor in the periphery of the lung and 58 patients (50% of the patients) who had a primary tumor in the central portion of the lung. Within this group of 120 patients, only 29 patients (24% of the patients) had PET-positive N1 disease. Only 16 out of 58 patients (28%) in the central group and only 13 out of 62 patients (21%) in the peripheral group had PET-positive N1 disease. There was no clinical or pathological difference between the patients who had PET-positive N1 disease and PET-negative N1 disease. The average maxSUV of the primary tumor was 13 ± 10.7 and average maxSUV of the PET-positive N1 disease was 6.3 ± 4.1. Kaplan Meier analysis showed that there was no significant difference in survival between the patients who had PET-positive N1 disease and PET-negative N1 disease.

      Conclusion
      Among patients with pathologic stage II non-small cell lung cancer, preoperative PET scan was very poor at predicting positive pathologic N1 disease. Since it is difficult to predict pN1 disease, operative patients with clinical stage I non-small cell lung cancer should have surgical resection oppose to ablative therapy. Moreover, SUV uptake of N1 disease in patients with pathologic stage II lung cancer did not predict worse survival in pathologic stage II patients. Thus, patients with cN1 disease should undergo surgical resection after appropriate mediastinal staging.