Is S-1 a potential game changer in adjuvant therapy of pancreatic cancer?

There remains a lack of consensus on the optimal adjuvant therapy for pancreatic cancer. In general, chemoradiation is favored in the United States and gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free survivals and in some studies overall survival. We present the summary of three abstracts from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting and discuss their potential impact on our clinical practice. Adjuvant oral chemotherapy with S-1 (Fukutomi et al., Abstract #4008) has now emerged as a promising alternative to the traditional gold standard of intravenous gemcitabine in a relatively large randomized phase III clinical trial. Another study by Yoshitomi et al. (Abstract #4056) examined the value of adjuvant chemotherapy with S-1 alone versus combination of S-1 and gemcitabine versus gemcitabine alone in a three arm phase II clinical trial (CAP-002 Study). In terms of biomarkers in pancreatic cancer, Neoptolemos et al. presented the impact of hENT1 tumor levels on the outcome of the patients with pancreatic cancer (Abstract #4006) who had received adjuvant chemotherapy with either 5-flurouracil or gemcitabine in the ESPAC trial.

A modified triple test for palpable breast masses: the value of ultrasound and core needle biopsy.

BACKGROUND: The original triple test score (TTS)--clinical examination, mammogram, and fine-needle aspiration (FNA) biopsy--has long been used to evaluate palpable breast masses. We modified the original TTS to include ultrasound (US) and core biopsy to determine their role in evaluating palpable breast masses. METHODS: A retrospective chart review of 320 female patients was performed. We developed a modified triple test score (mTTS) that included physical examination, mammogram and/or US, and FNA and/or core biopsy. For the examination and imaging score, 1-3 points were given for low, moderate, or high suspicion. Biopsy scores were characterized as benign, atypical, or malignant. Final outcome was determined by open biopsy or follow-up greater than 1 year. RESULTS: Physical examination was 92% accurate (95% confidence interval [CI] 0.89-0.96, p < 0.0001) at predicting whether a mass was benign or malignant. Imaging was 88% accurate (95% CI 0.84-0.92, p < 0.0001) and needle biopsy was 95% accurate (95% CI 0.92-0.98, p < 0.0001). The modified triple test was 99% accurate (95% CI 0.98-1.00, p < 0.0001). Each 1-point increment in the mTTS was associated with an increased risk of cancer, with an odds ratio of 9.73 (CI 5.16-18.4, p < 0.0001). For 150 patients, we compared the original TTS with the mTTS. US and core biopsy changed the scores of 24 patients; only three changed clinical management. CONCLUSIONS: For patients with a palpable breast mass and a mTTS score of 3-4, no further assessment is necessary. Those with a mTTS of 8-9 can proceed to definitive therapy. Patients with a mTTS of 5-7 require further assessment. US and/or core biopsy added little to the accuracy or predictive value of the original TTS.

The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer.

BACKGROUND: To determine the effect on margin evaluation for patients with breast cancer, we prospectively quantified the "flattening" of the breast specimen after surgical removal. METHODS: The volume and height of 100 consecutive breast biopsy specimens were recorded independently by the operating surgeon and the pathologist. Five factors were analyzed that were thought to contribute to changes in specimen dimensions: patient age, breast tissue density, mammographic lesion type, specimen size, and the use of compression during specimen radiography. RESULTS: After surgical removal, mean volume and height of the breast specimens decreased from 46 cm(3) to 29 cm(3) (30%) and from 2.6 cm to 1.4 cm (46%), respectively. Flattening of the breast specimens occurred in all subgroups studied. CONCLUSIONS: Breast specimens are flattened after surgical removal, losing almost 50% of their original height. This "pancake" phenomenon has important implications for the accuracy of margin analysis.

Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer.

PURPOSE: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. METHODS AND MATERIALS: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol. Eligible patients included those with T1, T2, N0, N1 (< or =3 nodes positive), and M0 tumors of nonlobular histologic features with negative surgical margins, no extracapsular lymph node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, reexcision, or either sentinel or full-axillary sampling. Direct visualization, surgical clips, and ultrasound and/or CT scan assisted in the delineation of the target volume, defined as the excision cavity plus a 2-cm margin. High-activity 192Ir (3-10 Ci) was used to deliver 340 cGy/fraction, 2 fractions/d, for 5 consecutive days, to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. RESULTS: The median follow-up of all patients was 33 months, and the mean patient age was 63 years. The mean tumor size was 1.3 cm, and 55% had an extensive intraductal component. Three patients had positive axillary nodes. Two patients experienced moderate perioperative pain that required narcotic analgesics. No peri- or postoperative infections occurred. No wound healing problems and no significant skin reactions related to the implant developed. The Radiation Therapy Oncology Group late radiation morbidity scoring scheme was applied to the entire 33-case cohort. In the assessment of the skin, 30 cases were Grade 0-1 and 3 cases were Grade 2. Subcutaneous toxicity was scored as 11 patients with Grade 0, 3 with Grade 1, 8 with Grade 2, 3 with Grade 3, and 8 with Grade 4. Clinically evident fat necrosis occurred in 8 patients at a median of 7.5 months after HDR brachytherapy completion. The only variables significantly associated with Grade 3-4 toxicity were the number of source dwell positions and the volume of tissue encompassed by the prescription isodose shell. The global cosmetic scores after a minimum of 18 months' follow-up were 0 cases with poor, 4 with fair, 5 with good, and 24 with excellent scores. One case of ipsilateral breast tumor recurrence was diagnosed 23 months after HDR brachytherapy, for a 4-year actuarial recurrence rate of 3%. This failure appeared to be a new primary tumor, because it was histologically distinct from the initial tumor and was located 9 cm from the initial tumor bed and 3 cm from the edge of the implant volume. CONCLUSION: Radiotherapy of the tumor bed alone with HDR interstitial brachytherapy is associated with a 33% incidence of Grade 3-4 s.c. toxicity, but with generally favorable overall cosmetic results. The risk of toxicity appears to be primarily related to the implant volume. With limited follow-up, the incidence of ipsilateral breast tumor recurrence was low.