Is there an Ethnic Predisposition to Developing Brain Metastases (BM) in Asian Patients with Colorectal Cancer?

BACKGROUND: Most common sites of metastases in patients with colorectal cancer (CRC) include liver and lung. Brain metastases are very rare but their presence is associated with a poor prognosis and shorter survival. We report our investigation into the impact of race/ethnicity on the incidence of BM in CRC patients. METHOD: We retrospectively reviewed patients diagnosed with CRC from 2010 - 2018 at a single institution and analyzed any association of development of brain metastases with race and ethnicity. Race and ethnicity were defined in accordance with federal standards set by the US Census. RESULT: We identified 264 CRC patients and 76(29%) were identified as Asian. Of those 76 patients, 5(7%) developed brain metastases. All 5 patients were male and stage IV at initial diagnosis. Brain metastases was a late stage phenomenon. Median time to development of brain metastases was 29 months (Range: 26 - 33). Median overall survival after BM diagnosis was 5.5 months (Range: 4 - 11). Overall survival was longest for the patient who had both radiation and surgery. CONCLUSION: Our study showed an incidence of brain metastases of 7% in the Asian sub-population compared to the historical control of 0.6% - 3.2% in the overall population. These results at the least warrant further investigation in a larger patient population of brain metastases in CRC patients with emphasis on molecular markers.

Is There any Survival Benefit of Maintenance Chemotherapy Following Adjuvant Chemotherapy in Patients with Resected Pancreatic Cancer Patients with Post-Surgery Elevated CA 19-9?

BACKGROUND: Pancreatectomy offers only potential for cure but is only possible in a minority of patients. Even in those patients who receive adjuvant chemotherapy, majority of them succumb to death due to metastases. Radiation Therapy Oncology Group 9704 showed that post-surgery CA 19-9 levels are an important predictor of survival. European study group for pancreatic cancer-3 showed that completion of all 6 cycles of adjuvant chemotherapy was an independent prognostic factor. Any survival benefit of an intensified chemotherapy strategy has not been demonstrated in patients with persistently elevated CA 19-9 following surgery. The object of this study was to investigate any benefit of maintenance chemotherapy following adjuvant in these patients. METHODS: Twenty patients with R0 surgery of pancreatic cancer who received adjuvant chemotherapy with post-surgery elevated CA 19-9 but no radiographic evidence of cancer was identified from 2005-2017. Either biopsy or positron emission tomography scan determined recurrence of cancer. Efficacy endpoints including overall survival and disease-free survival were assessed. RESULTS: Maintenance and additional chemotherapeutic agents included 5-FU, capecitabine, platinum agents, irinotecan and nab-paclitaxel. CA 19-9 normalized in 3 patients while 22 persisted to be elevated or had further increase in the marker. Two patients underwent metastatectomy. Median disease-free survival was 14.5m (9-18), OS 29m (19-96) and OS rates were 80%, 50% at 1 and 2 years respectively. CONCLUSIONS: We believe that the longer overall survival of our patients with elevated CA 19-9 post-surgery was due to maintenance and additional chemotherapy following planned 6-months of adjuvant therapy, close monitoring with monthly CA 19-9 and 3-monthly computed tomography scans. Our study also underlines importance of collecting pre-surgery CA 19-9 and complete staging including chest. Prospective study aiming to evaluate role of maintenance or intensified chemotherapy or targeted agents are indicated.

Chronic Use of Long-Acting Somatostatin Analogues (SSAs) and Exocrine Pancreatic Insufficiency (EPI) in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): An Under-recognized Adverse Effect.

Background: Somatostatin Analogues (SSAs) are used to treat Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and acromegaly. Side effects of SAAs usually include biliary disorders, gastrointestinal disorders, injection-site pain and hyperglycemia. Exocrine Pancreatic Insufficiency (EPI) is often misdiagnosed as disease progression or failure to SAAs or diagnosed after a delay in patients receiving SAAs. We present our experience with EPI developing in patients following use of SAAs. Methods: We reviewed chart and pharmacy records of 110 GEP-NETs patients who received SSAs. Data was collected including demographics, pathology, stage, dose/duration of long and short-acting SA, use of antidiarrheal, pancreatic enzyme replacement (PER), proton pump inhibitors (PPI) or H2 blockers). Laboratory data include chromogranin-A (CgA), urine 5-HIAA and quantitative fecal fat test (QFFT) or fecal elastase test (FE). EPI was defined by a FE below normal level OR by a reduction of ≥ 21.2% or steatorrhea on QFFT. Patients who were identified to develop EPI were treated with pancreatic exocrine replacement therapy (PERT). Results: Among, 110 GEP-NETs patients, 104 received LA Octreotide and 6 Somatuline Depot Injection. Of these, 23 received short-acting SSA for worsening diarrhea, 96 had intensification of antidiarrheal and 1 got telotristat ethyl. QFFT confirmed EPI in 19, 11 based on clinical symptoms, and 16 had sample error or refusal to collect specimen. CTCAE 4.0 grades of EPI were: grade 2(69%), grade 3(22%) and grade 4(9%). Median time to development of EPI was 12 months (95%CI 3 - 23). Except 1, all patients received PERT either with concomitant PPI (13) or later if no improvement with PERT (6) and 2 on H2 blockers. 37% of the patients had improvement in EPI within 4-8 weeks. Deficiency of vitamins and trace elements was found in 11 of 19 patients, who received supplementation. Conclusions: Our experience constitutes the first and the largest study addressing EPI as a rare but serious complication of chronic use of SAAs. Although SAAs are used to treat diarrhea, paradoxically they can worsen diarrhea secondary to EPI. Early recognition and diagnosis of this under-diagnosed and under-reported side effect of SAAs, such as EPI, can improve not only diarrhea and weight loss in these patients but also can reduce cost of using short-acting SAAs and antidiarrheal.

Treatment with Lanreotide Depot Following Octreotide Long-Acting Release Among Patients with Gastroenteropancreatic Neuroendocrine Tumors.

Objective: To examine patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who receive sequential treatment with somatostatin analogs. Materials and Methods: This retrospective chart review examined lanreotide depot/autogel tolerability and efficacy among GEP-NET patients who received lanreotide after octreotide long-acting release (LAR) at Tufts University Medical Center. Information obtained included background patient characteristics, dosing, adverse events (AEs), radiologic response, and biochemical markers. Results: Patients (n = 16; 43-81 years; mean age, 64.25 years; 11 female) with nonfunctional, low-grade GEP-NETs receiving octreotide LAR 30-60 mg were transitioned to lanreotide because of patient decision (n = 6), disease progression (n = 6), AEs (n = 2), poor tolerance (n = 1), and injection discomfort/pain (n = 1). Lanreotide doses started at 120 mg (n = 13), 90 mg (n = 1), or 60 mg (n = 2); 8 patients received concomitant therapies, mostly liver-directed (radiofrequency ablation/radioembolization). AEs associated with lanreotide experienced by ≥2 patients were fatigue, diarrhea, nausea, hypertension, pancreatic enzyme deficiency, and hyperglycemia. Radiologic treatment responses of the combination of lanreotide with other therapeutic modalities included complete response (n = 1), partial response (n = 5), and stable disease (n = 9). One patient had radiologic progression. Serum serotonin and chromogranin levels decreased, but urinary 5-hydroxyindoleacetic acid levels appeared relatively unchanged. Conclusion: Among post-octreotide GEP-NET patients, including those with disease progression or poor octreotide tolerance, lanreotide alone or with concomitant therapies was well tolerated and associated with radiologic responses.

Does "OPTINAB" strategy ("stop-and-go") work in treatment of advanced pancreatic cancer (APC) with nab-paclitaxel-gemcitabine?

BACKGROUND: MPACT demonstrated a survival benefit of nab-paclitaxel plus gemcitabine versus gemcitabine in advanced pancreatic cancer (APC). However, sensory peripheral neuropathy is a dose-limiting toxicity and neuromodulators have shown limited, if any activity in ameliorating neuropathy. In colorectal cancer, the OPTIMOX ("stop-and-go") approach offered a strategy to reduce neuropathy. No data exist to support this strategy for nab-paclitaxel in APC. METHODS: Retrospective study of APC patients who developed grade 3 neuropathy during nab-paclitaxel plus gemcitabine was done. Nab-paclitaxel was held and then reinstituted upon radiological or tumor marker progression. Duration of disease control (DCC) was measured. We named this strategy "OPTINAB". RESULTS: Seven patients out of 27 (25%) developed grade 3 neuropathy after an average of 4.2 months; nab-paclitaxel was suspended while gemcitabine was continued. Maintenance gemcitabine continued for a mean of 2.8 months. Upon progression (radiologic or CA19-9) nab-paclitaxel was re-instituted with gemcitabine. One patient could not tolerate nab-paclitaxel due to worsening of neuropathy while other six continued the combo with mean progression-free survival 2 (PFS2) of 2.2 months. The six patients continued nab-paclitaxel for a mean of PFS2 of 2.2 months (range 1-4 months). Nab-paclitaxel resulted in improvement of an average DDC with an average of (7.0 + 2.2 =) 8.2 months (range 8-13 months). Average overall survival for this group was 11.7 months (range 9.5-17 months). Reintroduction of nab-paclitaxel resulted in an average DDC of 9.4 months. Average overall survival (OS) for this group was 11.7 months. CONCLUSIONS: "OPTINAB" approach improved PFS2 in these patients and was feasible as majority of the patient tolerated nab-paclitaxel. Although it is a small study, it supports the need for a randomized, prospective study to test the concept of "OPTINAB".

Can patients with eating disorders learn to eat intuitively? A 2-year pilot study.

The present article reports on a 2-year pilot study that evaluated the effectiveness of an intuitive eating program for patients in an eating disorder treatment center. Standardized measures of intuitive eating and eating disorder and psychological symptoms were administered. Psychotherapists and dietitians rated patients on the healthiness of their eating attitudes and behaviors. Preliminary findings indicated that patients can develop the skills of intuitive eating, and that the ability to eat intuitively is associated with positive treatment outcomes for each diagnostic category (i.e., anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified). We conclude by offering recommendations about how to implement intuitive eating training safely and effectively in inpatient and residential treatment programs.

A theistic spiritual treatment for women with eating disorders.

The authors describe a psychological treatment for women with eating disorders who have theistic spiritual beliefs and illustrate its application with a case report. They begin by briefly summarizing a theistic view of eating disorders. Then they illustrate how a theistic approach can complement traditional treatment by describing the processes and outcomes of their work with a 23-year-old Christian woman receiving inpatient treatment for an eating disorder not otherwise specified and a major depressive disorder (recurrent severe).

Examining the relationship between religious orientation and eating disturbances.

The relationship between religion and eating concerns is receiving increasing empirical attention. The current investigation sought to examine the relationship between eating attitudes and religious orientation, utilizing the fourfold typology of religious orientation. A curvilinear relationship was found between religious orientation and eating attitudes among a subclinical college population and a clinical population of individuals receiving inpatient treatment for eating disorders, particularly among extrinsically orientated individuals with diagnosis of bulimia nervosa.