Journal Club

• Continuous Infusion, and Concurrent Radiotherapy in Patients With Locally Advanced Esophageal Cancer Produced a High Percentage of Long-Lasting Pathological Complete Response

• Cancer. 2012 Nov 16;[Epub Ahead of Print], F Pasini, G de Manzoni, A Zanoni, et al

Background

• This phase 2 study was aimed at defining the pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, continuous infusion (c.i.) of 5-fluorouracil (5-FU) and concomitant radiotherapy (RT) in untreated stage II-III adenocarcinoma and squamous cell carcinoma of mid-distal thoracic esophagus.

Methods

• The schedule consisted of a first phase of chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were as follows: docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50, and 57 plus 5-FU c.i. (180 mg/m2 on days 1-21 and 150 mg/m2 on days 29-63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after the completion of chemoradiation.

Results

• A total of 74 patients were enrolled; pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) (pnCR) in 15% of the patients (11 of 74). Grade 3-4 neutropenia, nonhematological toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients, respectively.

Results

• Median follow-up was 55 months (range, 3-108 months). Median survival of all 74 patients was 55 months, whereas it was not reached in the pCR subset.

• The 3- and 5-year survival rates were, respectively, 83% and 77% for pCR, 73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001).

Conclusion

• This study shows that 1) this intensive weekly schedule produced a high pathological response rate, 2) responders had high and long-term durable survival rates.

• Lapatinib Plus Capecitabine in Patients With Previously Untreated Brain Metastases from HER2-positive Metastatic Breast Cancer (LANDSCAPE): A Single-group Phase 2 Study

• Lancet Oncol. 2012 Nov 1;[Epub Ahead of Print], T Bachelot, G Romieu, M Campone, et al

Background

• Brain metastases occur in 30–50% of patients with metastatic HER2-positive breast cancer.

• In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT).

• Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer.

Methods

In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive metastatic breast cancer with brain metastases not previously treated with WBRT, capecitabine, or lapatinib.

• Treatment was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m2, orally) from day 1 to day 14

Methods

• The primary endpoint was the proportion of patients with an objective CNS response, defined as a 50% or greater volumetric reduction of CNS lesions in the absence of increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease. All responses had to be confirmed 4 weeks after initial response. Efficacy analyses included all patients who received the study drugs and were assessable for efficacy criteria.

Results

Between April 15, 2009, to Aug 2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21.2 months (range 2.2–27.6). 29 patients had an objective CNS response (65.9%, 95% CI 50.1–79.5); all were partial responses.

Results

• Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred.

Interpretation

• The combination of lapatinib and capecitabine is active as first-line treatment of brain metastases from HER2-positive breast cancer. A phase 3 trial is warranted.

• Benefit of Adjuvant Trastuzumab-Based Chemotherapy in T1ab Node-Negative HER2-Overexpressing Breast Carcinomas: A Multicenter Retrospective Series

• Ann Oncol. 2012 Oct 26;[Epub Ahead of Print], MJ Rodrigues, J Peron, J-S Frenel, et al

Background

• Randomized clinical trials showed the benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or >1 cm HER2+ breast carcinomas. No efficacy data have been published on ATBC in large series of pT1abN0 HER2+ tumors.

Patients and Methods

• This retrospective study evaluated 276 cases of pT1abN0 HER2+ breast tumors in eight French cancer centers. Factors associated with prognosis and ATBC prescription were analyzed.

Results

• A total of 129 cases (47%) were treated with ATBC (ATBC+), 19 with chemotherapy alone, 5 with trastuzumab alone, and 123 (45%) with neither trastuzumab nor chemotherapy (ATBC−). ATBC use was associated with the date of diagnosis (before or after June 2005) and with poor prognostic features. At a median follow-up of 44 months, there were 13 recurrences in the ATBC− group and 2 in the ATBC+ group. A

Results

• ATBC was associated with a significant survival benefit (99% 40-month disease-free survival for ATBC+ versus 93% for ATBC− cases; P = 0.018).

• Lack of hormone receptors (HRs) and the presence of lymphovascular invasion (LVI) were significantly associated with a poor prognosis and a greater benefit of ATBC

Conclusions

• ATBC was associated with a significantly reduced risk of recurrence in pT1abN0 HER2+ tumors, and was more beneficial in HR− and/or LVI+ tumors.

• Neoadjuvant Chemoradiotherapy for Patients With High-Risk Extremity and Truncal Sarcomas: A 10-year Single Institution Retrospective Study

• Eur J Cancer. 2012 Oct 22;[Epub Ahead of Print], NJ Look Hook, FJ Hornicek, DC Harmon, et al

Background

• Patients with large, high-grade extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of pre-operative chemotherapy consisting of mesna, adriamycin, ifosfamide and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and post-operative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this study is to assess outcomes in a recent cohort of patients treated on this regimen.

Methodss

We retrospectively reviewed records of 66 consecutive patients with STS of the extremity or trunk who were treated with the aforementioned regimen from May 2000 to April 2011. Clinicopathologic characteristics and patient outcomes were analysed.

Fig. 1

Source: European Journal of Cancer (DOI:10.1016/j.ejca.2012.10.002 )

Terms and Conditions

Results: Sixty-six patients were analysed and were equally divided between grade 2 and 3 tumours. Margins were negative in 57 (89%) patients and positive in seven (11%) patients. At a median follow-up of 46months, there were six (9%) locoregional and 20 (30%) distant recurrences. The locoregional and distant 5-year recurrence-free survival (RFS) rates were 91% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates

The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. Thirty-four (52%) patients had grade 3 or 4 acute haematologic chemotherapy-related toxicity. There were no statistically significant predictors of OS or RFS.

Conclusions: For a contemporary cohort of patients with high-risk extremity and truncal STS, a regimen of neoadjuvant chemoradiotherapy and surgery continues to result in high rates of survival with tolerable short- and long-term toxicity.

• Randomized Trial of Short-Course Radiotherapy Versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04

• J Clin Oncol. 2012 Sept 24;[Epub Ahead of Print], SY Ngan, B Burmeister, RJ Fisher, et al

• It is well established that adding radiotherapy to surgery has been shown to improve local control of rectal cancer. Short-course (SC) preoperative radiotherapy has demonstrated effectiveness over a long period in tumor control. More recently, long-course (LC) preoperative radiotherapy has demonstrated increased effectiveness in terms of local tumor control. Still, there is debate among clinicians about which approach provides better tumor control.

• The Trans-Tasman Radiation Oncology Group Trial 01.04 included 323 patients with clinical stage T3 rectal cancer who were randomly assigned to receive SC or LC preoperative radiotherapy. The median potential follow-up time was 5.9 years. The cumulative incidence of local tumor recurrence at 3 years was 7.5% for the SC group and 4.4% for the LC group (95% CI, –2.1%–8.3%; P = .24). The investigators noted that the risk of local tumor recurrence was lower for patients receiving LC but not statistically significant (hazard ratio for LC:SC, 0.75; 95% CI, 0.32–1.77; P = .66).

• It should be noted that 93 patients experienced a distant tumor recurrence either as a first or subsequent recurrence. The 5-year cumulative incidence rate of distant tumor recurrence was 27% for patients in the SC group and 30% for those in the LC group. In regard to distal tumors, there was a large (but not statistically significant) difference between treatments with respect to risk of local tumor recurrence, with 6 of 48 patients receiving SC and 1 of 31 patients receiving LC experiencing local tumor recurrence (hazard ratio for LC:SC, 0.26; 95% CI, 0.06–1.20; P = .26).

• Of interest, there was no difference demonstrated in overall survival (OS) between patients receiving SC and LC preoperative radiotherapy (5-year OS rates: SC group, 74%; LC group, 70%; hazard ratio for LC:SC, 1.12; 95% CI, 0.76–1.67; P = .62).

Epithelioid Sarcoma• Epithelioid sarcoma is a rare sarcoma that affects young adults with

an affinity to the distal upper extremity (hand and forearm). It mostly starts as a painless slow growing mass, but not uncommonly presents as a multifocal lesion. It has a high tendency for recurrence and spread along lymphatic channels. Biopsy is the diagnostic method of choice, with nodular, "pseudoganulomatous" formation with polygonal cells blended with spindle cells as the most common pattern seen microscopically. Loss of INI1 gene has been documented in majority of epithelioid sarcomas and may be used to confirm the diagnosis. Treatment primarily consists of wide resection. The role of adjuvants is debated. Male sex, tumor size more than 2 cm, proximal tumors and presence of vascular invasion in the microscopic specimen are correlated with worse clinical outcome.