PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. @*Materials and Methods@#We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. @*Results@#Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. @*Conclusion@#Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Treatment outcomes of curative radiotherapy in patients with vulvar cancer: results of the retrospective KROG 1203 study

PURPOSE: We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy. MATERIALS AND METHODS: Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients. RESULTS: During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size > or =3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (> or =70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically. CONCLUSION: Clinical size > or =3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age > or =70 years.

Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason. MATERIALS AND METHODS: The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence. RESULTS: The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively. CONCLUSION: Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.

Combined Primary Tumor and Extracranial Metastasis Status as Constituent Factor of Prognostic Indices for Predicting the Overall Survival in Patients with Brain Metastases

We retrospectively analyzed the prognostic factors on overall survival (OS) in patients with brain metastasis (BM) and evaluated the role of combined primary tumor and extracranial metastasis (ECM) status as a constituent factor for prognostic index. This study involved 897 patients with BMs who underwent radiotherapy between April 2003 and December 2009. Among the clinical parameters, multivariate analysis showed that age, Karnofsky performance status (KPS), combined primary tumor and ECM status, number of BMs, and treatment group were significant prognostic factors for OS (P < 0.05). To compare the discriminatory ability of 5 prognostic indices, i.e., recursive partitioning analysis (RPA), basic score for BMs (BSBM), score index for radiosurgery (SIR), graded prognostic assessment (GPA), and modified GPA including the combined primary tumor and ECM status (mGPA), the Akaike information criteria (AIC) were calculated. The mGPA showed the lowest AIC value, followed by RPA, GPA, SIR, and BSBM, in that order. It is implicated that modified score of pre-existing factors (i.e., age and KPS) and addition of the combined primary tumor and ECM status to the prognostic index can improve its discriminatory ability and the combined primary tumor and ECM status may be useful as one of constituent factors for prognostic index.

Sequential chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in patients with stage I/II extranodal natural killer/T-cell lymphoma, nasal type

BACKGROUND: The purpose of this report is to summarize our clinical experience of patients with stage I/II extranodal natural killer (NK)/T-cell lymphoma, nasal type, treated using sequential chemotherapy followed by radiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT). METHODS: Forty-three patients with stage I/II extranodal NK/T-cell lymphoma, nasal type, who received SCRT (16 patients) or CCRT (27 patients) were included in the present analysis. RESULTS: The median follow-up time was 39 months (range, 4-171 months) for all patients, 77 months (range, 4-171 months) for the SCRT group, and 31 months (range, 6-132 months) for the CCRT group. There were no statistically significant differences between the SCRT and CCRT groups with regard to the 3-year progression-free survival (PFS) (56% vs. 41%, P=0.823) and 3-year overall survival (OS) (75% vs. 59%, P=0.670). Univariate analysis revealed that patients with tumors confined to the nasal cavity and patients achieved complete remission had better PFS and OS rates, regardless of the treatment sequence. Multivariate analysis revealed that patients with tumors confined to the nasal cavity and patients aged < or =60 years had better OS rates. CONCLUSION: The effect of SCRT and CCRT are similar in terms of survival outcomes of patients with stage I/II extranodal NK/T-cell lymphoma, nasal type. Our results show that tumors confined to the nasal cavity and an age < or =60 years were associated with a better prognosis.

Long-Term Results of 2-Dimensional Radiation Therapy in Patients with Nasopharyngeal Cancer / 대한방사선종양학회지

PURPOSE: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). MATERIALS AND METHODS: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. RESULTS: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. CONCLUSION: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 2D conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

Intraoperative Radiation Therapy for Unresectable Pancreatic Cancer

PURPOSE: We wanted to evaluate the clinical effectiveness of intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) for treating unresectable or metastatic pancreatic cancer. METHODS: From August 1993 to July 2007, 28 patients with unresectable or metastatic pancreatic cancer received IORT (median: 20 Gy) combined with or without EBRT (median: 50.4 Gy). Eighteen patients were treated with IORT followed by EBRT, and 10 patients were treated by IORT alone. Eighteen patients underwent explolaparotomy and 10 patients underwent bypass surgery. RESULTS: The 1-year overall survival rate (OS) and the median survival time of all 28 patients were 21.4% and 7.5 months, respectively. The 1-year OS and median survival time for the clinical stage III patients were 33.3% and 10.2 months, respectively, and they were 7.7% and 5.1 months for the clinical stage IV patients, respectively (p=0.007). Univariate analyses revealed that the stage, chemotherapy and tumor volume were the significant prognostic factors for OS. The patients treated with IORT combined with EBRT had a more favorable 1-year local control rate than that of those patients treated with IORT alone (88.9% vs. 50.0, respectively, p=0.009). But the significant improvement in local control did not translate into a survival benefit. The addition of EBRT was an independent prognostic factor for improving the local control rate. The operative mortality was 0%. CONCLUSION: IORT combined with EBRT is considered to be effective in achieving local control and palliation for patients with unresectable or metastatic pancreatic cancer. Further, IORT seems to be safe and it does not increase the mortality or the incidence of surgical wound infection.