Efraim Idelevich

Is local excision after complete pathological response to neoadjuvant chemoradiation for rectal cancer an acceptable treatment option

PURPOSE: The role of local excision in patients with good histological response to neoadjuvant chemoradiation for locally advanced rectal cancer is unclear, mainly because of possible regional nodal involvement. This study aims to evaluate the correlation between pathological T and N stages following neoadjuvant chemoradiation for locally advanced rectal cancer and the outcome of patients with mural pathological complete response undergoing local excision. METHODS: This investigation was conducted as a retrospective analysis. Between January 1997 and December 2007, 320 patients with T3 to 4Nx, TxN+ or distal (≤6 cm from the anus) T2N0 rectal cancer underwent neoadjuvant concurrent chemoradiation followed by surgery. Radiotherapy was standard and chemotherapy consisted of common fluoropyrimidine-based regimens. RESULTS: After chemoradiation, 93% patients had radical surgery, 6% had local excision, and 3% did not have surgery. In the 291 patients undergoing radical surgery, the pathological T stage correlated with the N stage (P = .036). We compared the outcome of patients with mural complete pathological response (n = 37) who underwent radical surgery (group I) and those (n = 14) who had local excision only (group II). With a median follow-up of 48 months, 4 patients in group I had a recurrence and none in group II had a recurrence; one patient died in group I and none died in group II. Disease-free survival, pelvic recurrence-free survival, and overall survival rates were similar in both groups. CONCLUSION: In this retrospective study, nodal metastases were rare in patients with mural complete pathological response following neoadjuvant chemoradiation (3%), and local excision did not compromise their outcome. Therefore, local excision may be an acceptable option in these patients.

Early prediction of histopathological response of rectal tumors after one week of preoperative radiochemotherapy using 18 F-FDG PET-CT imaging. A prospective clinical study

BackgroundPreoperative radiochemotherapy (RCT) is standard in locally advanced rectal cancer (LARC). Initial data suggest that the tumor’s metabolic response, i.e. reduction of its 18 F-FDG uptake compared with the baseline, observed after two weeks of RCT, may correlate with histopathological response. This prospective study evaluated the ability of a very early metabolic response, seen after only one week of RCT, to predict the histopathological response to treatment.MethodsTwenty patients with LARC who received standard RCT regimen followed by radical surgery participated in this study. Maximum standardized uptake value (SUV-MAX), measured by PET-CT imaging at baseline and on day 8 of RCT, and the changes in FDG uptake (ΔSUV-MAX), were compared with the histopathological response at surgery. Response was classified by tumor regression grade (TRG) and by achievement of pathological complete response (pCR).ResultsAbsolute SUV-MAX values at both time points did not correlate with histopathological response. However, patients with pCR had a larger drop in SUV-MAX after one week of RCT (median: -35.31% vs −18.42%, p = 0.046). In contrast, TRG did not correlate with ΔSUV-MAX. The changes in FGD-uptake predicted accurately the achievement of pCR: only patients with a decrease of more than 32% in SUV-MAX had pCR while none of those whose tumors did not show any decrease in SUV-MAX had pCR.ConclusionsA decrease in ΔSUV-MAX after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned.

Prospective Phase II Study of Neoadjuvant Therapy with Cisplatin, 5-Fluorouracil, and Bevacizumab for Locally Advanced Resectable Esophageal Cancer

Background: We investigated the efficacy and tolerability of cisplatin and 5-fluorouracil (5-FU) plus bevacizumab as neoadjuvant therapy for patients with locally advanced resectable esophageal cancer. Patients and Methods: In this prospective phase II study, 22 patients with adenocarcinoma and 6 with squamous cell carcinoma received 2 4-day cycles of bevacizumab 7.5 mg/kg followed by cisplatin 80 mg/m2 infusion on day 1 followed by 5-FU 1,000 mg/m2 as a 96-h continuous infusion on days 1–4, separated by a 3-week interval. Results: The response rate was 39%, the R0 resection rate was 43%, and the median overall survival (OS) was 17 months. The regimen was well tolerated, with the most common severe toxicities being venous thromboembolism (10%), nausea, and gastrointestinal bleeding (7% each). In 37 patients previously treated with cisplatin and 5-FU alone at our institution and thus serving as historical controls, the response rate was 30%, the R0 resection rate was 44%, and the median OS was 23 months. There was no statistically significant difference between the 2 groups of patients. Conclusion: Adding bevacizumab to cisplatin and 5-FU neoadjuvant chemotherapy was active and well tolerated but did not seem to improve the resection rate or OS compared with prior regimens, including the historical controls at our institution.

Phase II study of UFT with leucovorin plus hepatic arterial infusion with irinotecan, 5-fluorouracil and leucovorin for non-resectable liver metastases of colorectal cancer.

Background: Compared with systemic therapy, hepatic arterial infusion (HAI) increases the response to fluoropyrimidines. Methods: Thirty-one patients with non-resectable, colorectal cancer (CRC) liver metastases received irinotecan 120 mg/m2, followed by leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 500 mg/m2 administered by HAI every 2 weeks, plus UFT (tegafur-uracil) 200 mg/m2/day with LV 30 mg/day on days 1–22, followed by a 6-day rest. Results: The objective response rate was 65% (all 20 patients achieving a partial response). Ten patients (32%) had stable disease. The median time to progression (TTP) and overall survival (OS) were 12 and 36 months. OS was similar in patients with low versus high expression of thymidylate synthase (TS) and/or dihydropyrimidine dehydrogenase (DPD). The regimen was well tolerated. Conclusions: UFT with LV plus HAI irinotecan and 5-FU/LV was a feasible and effective treatment for non-resectable CRC liver metastases, increasing response, TTP and OS. TS and DPD levels in liver metastases did not predict outcome.

Oncogenes in male breast cancer

The objective of this study was to assess the degree of expression and prognostic significance of c-erbB-2, p53, and bcl-2 in male breast cancer (MBC). Thirty male patients with the diagnosis of adenocarcinoma of the breast were studied retrospectively. All patients underwent surgery; c-erbB-2, p53, and bcl-2 were immunohistochemically stained on sections from formalin-fixed, paraffin-embedded tissues. Seventeen (56.7%) of the 30 cases of MBC were bcl-2 positive. Few specimens were found positive for c-erbB-2 (6.7%) and p53 (6.7%). The 5-year survival rate was marginally better for those patients with tumors staining positively for bcl-2 (p = 0.05). It was impossible to estimate the association between survival rate and p53 and c-erbB-2 expression because of the small number of positively stained specimens. In this study, only bcl-2 showed marginal association to other tumor parameters and a trend toward a better 5-year survival rate. At present there is inadequate evidence to support the use of molecular markers as independent prognostic markers in MBC.

Comparative study of the role of serum levels of p53 antigen and its tumor cell concentration in colon cancer detection

The role of serum levels of p53 antigen in detection of colon cancer was studied in different groups of cancer and noncancer patients and was compared with the results of immunohistochemical analyses. The p53 antigen was isolated from the human serum as a cytoplasmic fraction using the recently described new type of columns for affinity chromatography, gel fiberglass columns (Zusman and Zusman, 1995). Its concentration was detected by high performance liquid chromatography. The serum level of the p53 antigen significantly increased in cancer patients (3.6 mg ml(-1)) as compared to its concentration in patients with benign tumors (1.7 mg ml(-1)) or in patients with noncancer disorders (0.49 mg ml(-1)), and this was found to be a result of higher concentration of p53 protein in tumor cells. Coefficient of correlation between cellular concentration of p53 protein and its serum level was 0.44 in noncancer lesions and 0.48 in cancer patients. Serum levels of p53 antigen was shown to be highly active either in patients with noncancer lesions or in patients with cancer (r = 0.46 and 0.51 respectively), whereas the cell determination of p53 protein was effective only among noncancer patients (r = 0.61) but not in cancer patients (r = 0.22). The findings suggests that serum determination of p53 antigen can perhaps reveal this oncoprotein already in the early stages of cancer or even predict the putative development of cancer. The possibility to use the serum-levels of p53 antigen in the follow up patients with chronic diseases and to detect transformation of these diseases into cancer, or monitoring former cancer patients in order to detect as early as possible the incidence of recurrent cancer is discussed.

Gastric cancer: Biology and clinical manifestations in Israel

Gastric cancer (GC) in Israel remains incompletely characterized. The aim of this study was to define the clinical and pathological characteristics of GC in Israel and to compare them to the general Western population.

Phase II study of cisplatin, epirubicin, UFT, and leucovorin (PELUF) as first-line chemotherapy in metastatic gastric cancer

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur–uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided doses on days 1–22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24–52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5–7.5 months); overall survival was 9.5 months (95% CI 8.5–13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.

Impact of the 12-Gene Colon Cancer Assay on Clinical Decision Making for Adjuvant Therapy in Stage II Colon Cancer Patients

OBJECTIVES To evaluate the impact of the 12-gene Colon Cancer Recurrence Score Assay-a clinically validated prognosticator in stage II colon cancer after surgical resection-on adjuvant treatment decisions in T3 mismatch repair proficient (MMR-P) stage II colon cancer in clinical practice. METHODS This retrospective analysis included all patients with T3 MMR-P stage II colon cancer (Clalit Health Services members) with Recurrence Score results (time frame January 2011 to May 2012). Treatment recommendations pretesting were compared with the treatments received. Changes were categorized as decreased (to observation alone/removing oxaliplatin from the therapy) or increased (from observation alone/adding oxaliplatin to the therapy) intensity. RESULTS The analysis included 269 patients; 58%, 32%, and 10% of the values were in the low (<30), intermediate (30-40), and high (≥41) score groups, respectively. In 102 patients (38%), treatment changed post-testing (decreased/increased intensity 76/26 patients). The overall impact was decreased chemotherapy use (45.0% to 27.9%; P < 0.001). Treatment changes occurred in all score groups, but more frequently in the high (change rate 63.0%; 95% confidence interval [CI] 42.3%-80.6%) than in the intermediate (30.6%; 95% CI 21.0%-41.5%) and low (37.6%; 95% CI 30.0%-45.7%) score groups. The direction of the change was consistent with the assay result, with increased intensity more common in higher score values and decreased intensity more common in lower score values. CONCLUSIONS Testing significantly affected adjuvant treatment in T3 MMR-P stage II colon cancer in clinical practice. The study is limited by its design, which compared treatment recommendations pretesting to actual treatments received post-testing, lack of a control group, and nonassessment of confounding factors that may have affected treatment decisions.

Nasopharyngeal carcinoid tumor : Successful therapy for a tumor in a unique location

Carcinoid tumors are rare, especially in the head and neck; however, they mainly occur in the larynx and middle ear. To our knowledge, the existence of primary well-differentiated neuroendocrine (carcinoid) tumor in the nasopharynx has never been published before. Because of its unique location, the treatment of nasopharyngeal carcinoid tumor is challenging, and favorable outcome correlates with early diagnosis and surgical excision. We describe an elderly patient treated with combined external beam radiation and cold somatostatin analogue, for primary carcinoid tumor of the nasopharynx. Thirty-six months after diagnosis, the patient is alive with no evidence of disease progression. This case was approved by Institutional Review Board of our hospital. A 68-year-old man presented with a 4-month history of nasal obstruction and rhinorrhea, without epistaxis or any other complaints. Medical and surgical histories were unremarkable. Physical examination revealed a large nasopharyngeal mass covered by normal mucosa that obstructed the nasopharyngeal space. There was no evidence of serous otitis media or cervical lymphadenopathy. Cranial nerve examination at presentation was normal (at least II to X). T2 -weighted magnetic resonance images demonstrated a nasopharyngeal lesion that measured 3.4 4 cm, and involved the posterior nasal cavity and infiltrated sphenoid and posterior ethmoid sinuses, and cavernous sinus bilaterally (Fig 1). Nasopharyngeal biopsy revealed a well-differentiated tumor with a low proliferation index of ki-67 2%. Immunoperoxidase stain for chromogranin, neuron specific enolase, and synaptophysin shows prominent cytoplasmic reactivity. Vimentin stain was not expressed. Indium 131 labeled somatostatin receptor scintigraphy combined with computed tomography scans detected pathologic uptake in the nasopharynx, sphenoid sinus, and clivus without pathologic uptake elsewhere (Fig 2), subtype 2 and 5 somatostatin-receptors were over expressed. Due to the extensive skull base involvement, the tumor was determined to be unresectable, and the patient was referred for treatment with long-acting octreotide and radiotherapy. Neurophthalmologic follow-up 6 months after diagnosis revealed superior bitemporal quadrianopsia that could correlate with tumor pressure over the optic chiasm. Under the previously mentioned treatment, this finding did not progress. Follow-up MRI after 18, 24, and 36 months of treatment revealed no significant change in the size of the tumor mass.