Philip A. DeSimone

The Role of Thymectomy in Red Cell Aplasia

Red cell aplasia is an unusual cause of anemia. Fifty percent of all patients with red cell aplasia will have a thymoma. Twenty-five to 30% of those who undergo thymectomy will be cured. Data are presented that suggest that any patient with red cell aplasia should have thymectomy through a median sternotomy. One of 3 such patients who underwent the operation has had complete remission for two years.

Dose-escalation study of ICA-17043 in patients with sickle cell disease.

Study Objective. To determine the dose tolerance, safety, and pharmacokinetics of a single oral dose of ICA‐17043 in patients with sickle cell disease.

Cancer Family History Reporting: Impact of Method and Psychosocial Factors

Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis, risk assessment, prevention and treatment. However, research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports. The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies. Oncology patients (n=104) were administered a survey to assess psychosocial factors (i.e., information-seeking, worry, perceived risk, and health literacy) and were asked to provide family history in a written and an interview form. Randomization determined which form individuals received first. No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method. Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis. In sum, this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably. The ability to use written methods will facilitate collection of basic family history information in the oncology clinic.

Cancer Recurrence Worry, Risk Perception, and Informational-Coping Styles Among Appalachian Cancer Survivors

Despite a growing literature on the psychosocial impact of the threat of cancer recurrence, underserved populations, such as those from the Appalachian region, have been understudied. To examine worry and perceived risk in cancer survivors, Appalachian and non-Appalachian cancer patients at an ambulatory oncology clinic in a university hospital were surveyed. Appalachians had significantly higher worry than non-Appalachians. Cancer type and lower need for cognition were associated with greater worry. Those with missing perceived risk data were generally older, less educated, and lower in monitoring, blunting, and health literacy. Additional resources are needed to assist Appalachians and those with cancers with poor prognoses (e.g., liver cancer, pancreatic cancer) to cope with worry associated with developing cancer again. More attention for cancer prevention is critical to improve quality of life in underserved populations where risk of cancer is greater.

A Phase I Study of 7-t-Butyldimethylsilyl-10-Hydroxycamptothecin in Adult Patients with Refractory or Metastatic Solid Malignancies

Purpose: 7-t-Butyldimethylsilyl-10-hydroxycamptothecin (AR-67) is a novel third generation camptothecin selected for development based on the blood stability of its pharmacologically active lactone form and its high potency in preclinical models. Here, we report the initial phase I experience with i.v. AR-67 in adults with refractory solid tumors. Experimental Design and Methods: AR-67 was infused over 1 hour daily five times, every 21 days, using an accelerated titration trial design. Plasma was collected on the 1st and 4th day of cycle 1 to determine pharmacokinetic parameters. Results: Twenty-six patients were treated at nine dosage levels (1.2-12.4 mg/m2/d). Dose-limiting toxicities were observed in five patients and consisted of grade 4 febrile neutropenia, grade 3 fatigue, and grade 4 thrombocytopenia. Common toxicities included leukopenia (23%), thrombocytopenia (15.4%), fatigue (15.4%), neutropenia (11.5%), and anemia (11.5%). No diarrhea was observed. The maximum tolerated dosage was 7.5 mg/m2/d. The lactone form was the predominant species in plasma (>87% of area under the plasma concentration-time curve) at all dosages. No drug accumulation was observed on day 4. Clearance was constant with increasing dosage and hematologic toxicities correlated with exposure (P < 0.001). A prolonged partial response was observed in one subject with non–small cell lung cancer. Stable disease was noted in patients with small cell lung cancer, non–small cell lung cancer, and duodenal cancer. Conclusions: AR-67 is a novel, blood-stable camptothecin with a predictable toxicity profile and linear pharmacokinetics. The recommended phase II dosage is 7.5 mg/m2/d five times every 21 days. Clin Cancer Res; 16(2); 673–80

Defining the optimal timing of adjuvant therapy for resected pancreatic adenocarcinoma: A statewide cancer registry analysis

Long‐term results of the ESPAC‐3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic ductal adenocarcinoma (PDAC), early initiation (within 8 weeks) may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the OS impact of early versus late AT in a statewide analysis.

Ring appearance on Tc-99m MIBI thoracic SPECTs and increased uptake on Tc-99m HMDP thoracic SPECTs in a pulmonary mass of small cell carcinoma

Tc-99m MIBI is taken up avidly by viable tumor tissue and does not accumulate in the necrotic carcinoma. We present a patient who underwent Tc-99m MIBI and Tc-99m HMDP thoracic SPECTs: a large area of increased MIBI uptake with central photopenia (ring appearance) in the right upper lung localizes bone imaging agent and does not localize multiple areas of intense uptake in the metastatic hilar mediastinum lymph nodes. Rapid growth of tumor cells in the lung leading to central necrosis/ischemia accounts for bone imaging agent localization in the tumor, as well as the ring-appearance of lung mass on Tc-99m MIBI imaging. These findings may reflect less viability of the lung tumor as compared with intense MIBI uptake in hilar/mediastinal lymph node uptake without bone agent localization.

NeoadjuvantNab-paclitaxel and Gemcitabine in Borderline Resectable or Locally Advanced Unresectable Pancreatic Adenocarcinoma in Patients Who Are Ineligible for FOLFIRINOX

Background/Aim: Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX. Patients and Methods: This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery. Results: Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease. Conclusion: In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.

Paclitaxel, carboplatin, and capecitabine (TCX) with and without radiation in locally advanced and metastatic distal esophageal and esophagogastric junction cancer: A single-center retrospective review.

197 Background: Toxicities of the active triple-drug DCF regimen (docetaxel, cisplatin and 5-FU) in gastric cancer limit its broad use and general acceptance as first-line therapy. To improve the toxicity profile of triple-drug therapy, distal esophageal and esophagogastric junction (DE-EGJ) poorly differentiated and moderately differentiated adenocarcinoma patients were treated with TCX. This single-center retrospective review is reported for patients treated between 2005 and 2013. Methods: Patients with DE-EGJ adenocarcinoma were treated with capecitabine (850 mg/m2 5 out of 7 or 14 out of 21 days), carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 3 weeks. Those with locally advanced disease received concomitant radiation therapy (50.4 Gy using 3D approach) during the first 2 cycles. Dose reductions (25-50%), delay of therapy and hospitalizations for disease and treatment-related Grades 3/4 toxicities were recorded. Growth factors were prescribed reactively. Kaplan-Meier statistics were used for sur...

The natural history and effect of adjuvant therapy on resected AJCC stage I-II lymph node-negative pancreatic cancer.

264 Background: Previous investigation has suggested that early stage, lymph node negative pancreatic adenocarcinoma (PAC) has a relatively good prognosis and adjuvant therapy provides little benefit over surgery alone. The purpose of our trial was to evaluate patients with stage I-II PAC receiving surgical resection to determine their clinical characteristics, overall outcome, and the impact of adjuvant therapy on survival. METHODS Utilizing the population-based registry data from the Kentucky Cancer Registry (KCR) we identified patients with lymph node negative, AJCC I-II, PAC who underwent pancreatic resection during the years of 1995-2008. Patients were further stratified by receipt of surgery alone versus surgery with adjuvant chemotherapy or chemoradiation. Clinical and pathologic data included patient demographics, tumor characteristics, and lymph node status. Kaplan-Meier and Cox-regression survival analyses were performed. RESULTS During the study period, 203 patients meeting criteria were identified from the KCR. Median survival (MS) for the entire cohort was 21.7 months. The majority of patients were >70 years old, Caucasian, had well or moderately differentiated tumors and tumors <5cm. 46% (n=94) and 54% (n=109) of patients had stage I and II disease respectively. When stratified by surgery only (n=119, 59%) versus adjuvant therapy (n=84, 41%), only younger age predicted receipt of adjuvant therapy (p=0.002). Adjuvant therapy provided no benefit over surgery alone regardless of stage (stage I MS: 21.5 vs. 24.7 months, p=0.97 and stage II MS: 24.2 vs. 18.0, p=0.13, respectively). By multivariate analysis, only tumor size >5cm predicted worse survival (HR 2.32, CI 1.21-4.45, p=0.012). Age, stage, adjuvant therapy, differentiation, and lymph node retrieval had no impact on survival. CONCLUSIONS Our data indicate that the survival for surgically resected early stage, lymph node negative pancreatic adenocarcinoma remains poor and is not improved by the addition of adjuvant chemotherapy. These findings should be considered when designing future adjuvant therapy trials for this deadly disease.