Saikrishna Yendamuri

Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

PURPOSE To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. METHODS AND MATERIALS Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. RESULTS Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving ≥10 Gy (V(10)), 15 Gy (V(15)), and 20 Gy (V(20)) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V(10), V(15), and V(20) to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. CONCLUSIONS Significant detriments in PK size and renal function were seen after abdominal RT. The V(10), V(15), and V(20) were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

Phase II Study of Perioperative Chemotherapy with Cisplatin and Pemetrexed in Non-Small-Cell Lung Cancer

Introduction: Pathologic complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated pCR rate of cisplatin with pemetrexed in non–small-cell lung cancer. Methods: Patients with stages IB to IIIA non–small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1 were enrolled in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of more than or equal to 10%. Pretreatment mediastinal lymph node biopsy was required. Patients received three cycles of cisplatin 75 mg/m2 with pemetrexed 500 mg/m2 (day 1 every 21 days) preoperatively and additional two cycles within 60 to 80 days after surgery. The primary end point was pCR. Polymorphisms in FPGS, GGH, SLC19A1, and TYMS genes were correlated with treatment outcomes. Results: Thirty-eight patients were enrolled, with median age of 62.5 years. Preoperatively, 26% had squamous histology, and 34% had biopsy-proven N2 involvement. R0 resection was achieved in 94% of the 34 patients who underwent surgery, and 54% had documented N2 clearance. There was no pCR seen. Median disease-free survival (DFS) and overall survival of these patients have not yet been reached in contrast to median of 13.8 and 24.2 months, respectively, in patients with persistent N2 disease (p = 0.3241 and p = 0.1022, respectively). There was a statistically significant association between DFS and postoperative tumor, node, metastasis stage (p = 0.0429), SLC19A1 rs3788189 TT genotype (p = 0.0821), and viable tumor defined as less than or equal to 10% of resected specimen (p = 0.026). Conclusion: The primary end point was not met. Patients with N2 clearance, less than or equal to 10% viable tumor in the resected specimen, and SLC19A1 rs3788189 TT genotype have favorable DFS outcomes.

Sclerosing Pneumocytoma with Lymph Node Metastasis

A 33-year-old woman with a family history of multiple cancers had been undergoing surveillance scans. Magnetic resonance imaging revealed cysts in the kidney and pancreas, multiple hemangiomas in the liver, and a lesion in the left lower lobe (LLL) of the lung. Repeat positron emission tomogram/computed tomography demonstrated a 1.8 1.6-cm nodule (Fig. 1) within the LLL. The patient underwent endobronchial ultrasound– guided fine needle aspiration biopsy of the LLL nodule, which showed hypercellular smears containing uniform, cuboidal, round, and oval medium-sized cells. They were diffusely positive for thyroid transcription factor-1, and negative for neuroendocrine cell markers. The diagnosis was well-differentiated lung adenocarcinoma. The patient underwent video-assisted thoracoscopic LLL lobectomy, which showed a well-circumscribed 2.5-cm yellow-tan nodule composed of mostly monomorphic, cuboidal surface cells and round cells with pink to clear cytoplasm and well-defined cell borders in papillary, solid, and sclerotic growth patterns. Occasional hemorrhagic foci were also present. A focal area of mild cytologic atypia was noted. A focus of metastatic tumor deposit containing solid sheets of cells was identified in one of the peribronchial lymph nodes. The results of staining for thyroid transcription factor-1 and epithelial membrane antigen were positive in both surface and round cells, but cytokeratin 7 and cytokeratin AE1/AE3 stained only surface cells (Fig. 2). The cytomorphologic examination findings and immunoprofile were consistent with sclerosing pneumocytoma (SP) with a lymph node metastasis. SP (previously called sclerosing hemangioma) is a rare tumor of the lung that is thought to arise from primitive respiratory epithelium. This tumor usually occurs in middle-aged adults with a male-to-female ratio of 1:5. 1 Surgical resection is curative without a need for additional treatment. Although SP is considered a benign tumor, we found a lymph node (LN)

The effect of smoking history on response and survival outcomes patients with in esophageal cancer treated with neoadjuvant concurrent chemoradiotherapy followed by surgery.

e14601 Background: There is limited information on the impact of current or former smoking status on survival outcomes in esophageal cancer patients treated with trimodality therapy. METHODS Patients with esophageal carcinoma who completed neoadjuvant concurrent chemoradiotherapy and underwent surgical resection between October 2002 and April 2010 at Roswell Park Cancer Institute were analyzed. Smoking history was abstracted from consultation notes at initial presentation. Survival was compared between patients with any self-reported history of smoking (current or former smokers) and patients who denied any prior history of smoking (never smokers). Follow up was calculated from the date of diagnosis to the date of death or last follow up. Unknown disease status was categorized as a recurrence. Unpaired t-tests were used for statistical comparisons. RESULTS A total of 115 patients were analyzed, of whom 11% were female and 77% of patients reported a current or former history of smoking. There was no difference in histology, mean radiotherapy dose delivered, chemoradiotherapy completion time, pathologic complete response rates, or total follow up time between groups. Never smokers had a much higher proportion of women as compared with current or former smokers (30.8% vs. 5.6%, p=0.0003). With a median follow-up time of 28 months, there was no difference in disease recurrence, disease specific mortality, or overall survival by self-reported smoking status (current or former vs. never smokers). CONCLUSIONS In esophageal cancer patients receiving neoadjuvant concurrent chemoradiotherapy followed by surgery, data suggest that a history of current or former smoking has no impact on pathologic complete response, recurrence, or survival. Analyses may be confounded by a higher proportion of women in the never smoking population.

Abstract A21: Lung cancer surveillance with CT scan and autofluorescence bronchoscopy

Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the survival rate is less than 15%. Sputum cytology, x‐ray and CT scan have been evaluated as screening tools for early lung cancers, without much success. Auto‐fluorescence bronchoscopy (AFB) has been recently shown to be effective in diagnosing central bronchial cancers. Combined surveillance with both spiral CT scan and AFB might help to increase the detection rate of the both central and peripheral lung cancers. Methods: The study included 205 patients who were enrolled in the High Risk Lung Cancer Surveillance Cohort at Roswell Park Cancer Institute (RPCI) with at least 2 of the following risk factors: (1) radiographically documented pulmonary asbestosis or; (2) a history of previously treated aero‐digestive cancer or; (3) > 20 pack years smoking history or; (4) COPD with an FEV1 Results: A total of 20 invasive cancers/CIS were diagnosed in the 205 patients. Seven were diagnosed at baseline, 4 within 1 year of enrollment and 9 on follow up of more than 1 year. Between them, AFB and CT scan diagnosed all baseline cancers. Only 3/7 cancers were detected on x‐ray screening and only 1/7 patients demonstrated atypia on sputum cytology. Overall, 17 invasive cancers and 3 CIS were diagnosed during the surveillance study. All the 3 CIS were identified only on AFB. Of the 17 invasive cancers, CT scan detected 15 cancers (88%) and AFB detected 5 of these cancers (30%). CT scan showed a 67% relative increase in sensitivity for detecting prevalent cancers and 3 times greater sensitivity for incident and prevalent cancers compared to x‐ray screening. CT scan and AFB detected 19 of the 20 CIS/cancers (95%), whereas x‐ray and sputum cytology together detected only 5/20 CIS/cancers (25%). The sensitivity of CT scan and AFB in diagnosing pre‐malignant lesions and cancers improved by almost two and half times relative to x‐ray and sputum. Conclusion: The addition of AFB exam to yearly spiral CT scan of the chest could be a more efficient surveillance tool to identify early stage lung cancers, both in the central and peripheral lung. A greater efficiency and cost effectiveness can be achieved by limiting the use of the combination of AFB and CT scan in very high risk patients, selected based on their exposures and risk factors. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A21.

Abstract A22: Spirometric surveillance for premalignant and malignant bronchial lesions

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are diseases that share common risk factors. It has been reported that more than half of the patients diagnosed with LC also suffer from COPD. Although COPD is a well known risk factor for LC, the relationship between impaired lung function (LF) and the incidence and progression of pre‐malignant lesions (PMLs) in the central airways is still unclear. Methods: The study included 217 high‐risk patients from a hospital‐based lung cancer surveillance cohort who underwent bronchoscopy with endobronchial biopsy of suspicious lesions, at the Roswell Park Cancer Institute, Buffalo, New York. All patients had lung function measurement within 6 months preceding their baseline biopsy. Baseline histopathology diagnoses included 91squamous metaplasia (SM), 25 squamous dysplasia (SD), 1 in‐situ carcinoma and 5 invasive bronchial carcinoma. Follow‐up bronchoscopy and biopsy were performed on 69 patients. Sixteen patients had a progression of the baseline lesion to a higher grade. The relationship between the baseline LF measures and the incidence and progression of PMLs were examined using regression models. Results: Patients with forced expiratory volume in 1 second percent predicted (FEV1%) of Conclusion: Impaired LF can be a good predictor of occurrence and progression of PMLs in central airways of high risk patients. Spirometric measurement of lung function can be used as an additional tool for identifying target populations in need of more aggressive LC surveillance. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A22.