High-dose radiotherapy to 78 Gy with or without temozolomide for high grade gliomas

Objectives To describe outcomes associated with high-dose radiotherapy with and without temozolomide for high grade central nervous system (CNS) neoplasms. Methods Retrospective chart review of 60 patients diagnosed with malignant glioma treated with ≥70 Gy radiotherapy. Results Median age at diagnosis was 52 years, and 52 patients had astrocytomas (38 glioblastomas). Median prescribed radiotherapy dose was 78 Gy (range 70–80), and 29 patients received concurrent temozolomide. Eighty-six percent completed the planned course treatment. Three patients experienced RTOG grade 3 acute CNS toxicity; late brain necrosis was suspected in four patients. Overall median survival was 13 months (range 2–83). Within glioblastoma patients, temozolomide provided a statistically significant survival improvement over no chemotherapy (median survival 12.7 vs. 7.5 months; P = 0.0058). Conclusions High dose conformal radiotherapy to ≥70 Gy with chemotherapy for high-grade CNS neoplasms appears safe but survival remains suboptimal. Within glioblastoma patients, temozolomide provided statistically significant survival improvement over no chemotherapy.     

Early or delayed radiosurgery for WHO grade II astrocytomas

To evaluate the role of gamma knife stereotactic radiosurgery (SRS) in the management of newly diagnosed (early) or progressive (delayed) WHO grade II astrocytomas, the authors reviewed 25 patients who underwent SRS for pathologically proven WHO grade II astrocytomas between 1987 and 2009 at the University of Pittsburgh. The median patient age was 30 years (range 8–68 years). Sixteen patients had early SRS after stereotactic biopsy (n = 14), resection (n = 1) or radiation therapy (n = 1), and 9 underwent delayed SRS for progression after surgical resection (n = 3), radiation therapy (n = 4) or both (n = 2). The median tumor volume was 3.7 cm³ (range 0.6–17.0 cm³) and the median margin dose was 14 Gy (range 11–20 Gy). At a median of 65 months of follow-up (range 6–208 months), tumor control was observed in 13 patients (52%). The progression-free survival rates after SRS at 1, 5 and 10 years were 91.3, 54.1 and 37.1%, respectively. On both univariate and multivariate analysis smaller tumor volume (<6 cm³), higher marginal dose (≥15 Gy) and absence of contrast enhancement on imaging studies were associated with better progression free-survival. Gamma knife SRS is an additional option for patients with small volume, deep seated, non-enhancing and well-demarcated WHO grade II astrocytomas and does not preclude later conventional fractionated radiation therapy, cyst aspiration, or cautious debulking if feasible. It may also benefit patients with residual or recurrent tumors that have progressed after surgery, radiation therapy or both.     

Toxicity and early clinical outcomes in cervical cancer following extended field helical tomotherapy to para-aortic lymph nodes

PurposeTo evaluate toxicity and early disease outcome among patients treated for cervical cancer with extended-field helical tomotherapy to the para-aortic nodes.Patients and methodsThirty-eight patients (International Federation of Gynecology and Obstetrics [FIGO] stage IB2–IVA) from four institutions received extended-field helical tomotherapy and were retrospectively evaluated. All had nodal disease. Para-aortic lymph nodes were involved in 31 patients. Patients were assessed for toxicity using version 4 of the National Cancer Institute's common terminology criteria for adverse events. Survival curves were plotted using Kaplan-Meier estimates.ResultsAll patients underwent radiation to the tumor region (median dose: 45 Gy; range: 44–66 Gy), pelvic lymph nodes and para-aortic lymph nodes (median dose: 45 Gy; range: 44–60 Gy). The median dose to positive lymph nodes was 55 Gy (range: 45–65 Gy). All received platinum-based chemotherapy (31 concurrently). The median follow-up was 15 months. Acute toxicity events observed included one patient with grade 5 febrile neutropenia, 11 patients (29%) with grade 3 hematologic complications. Grades 3–4 gastrointestinal and genitourinary toxicities occurred in six (16%) and four (11%) patients, respectively. Three patients had grade 3 pelvic pain (8%). The 6- and 18-month overall survival rates were 94.7 and 63.9%, respectively. The 18-month locoregional control, disease-free survival, and late grade 3 toxicity rates were 60.2, 43.3 and 7.3%, respectively.ConclusionExtended-field helical tomotherapy was associated with low rates of acute gastrointestinal and genitourinary toxicities with early survival and locoregional control similar to other published series.     

Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study

We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46–72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5–34.5 months). The median tumor volume was 13.6 cm³ (range 1.2–45.1 cm³) and the median margin dose of GKSR was 16 Gy (range 13–18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6–28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5–23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1–25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.     

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8–60). The median follow-up for surviving patients was 4.8 years (range, 1.3–8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.     

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42–75 years) were enrolled. Both cisplatin (40 mg/m²) and vinorelbine (20 mg/m²) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6–93.4%). The median survival time was 23 months (range, 4–43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3–4 neutropenia in 84.6% of patients, grade 3–4 thrombocytopenia in 3.8%, and grade 3–4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3–4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. Conclusion: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.     

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT)

PurposeTo determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT).Materials and methodsThe dosimetric study was performed on patients receiving normofractionated (NFRT - 50 Gy in 25 fractions) or hypofractionated (HFRT - 40 Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes ± axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16 Gy and 10 Gy to the tumour bed, respectively.ResultsSixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8 Gy, 41.0 Gy and 44.4 Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2 Gy, 33.0 Gy and 34.9 Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively.ConclusionThe axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.     

Mid-course thoracic radiotherapy with cisplatin-etoposide chemotherapy in limited-stage small-cell lung cancer

Combination chemoradiotherapy is a standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, there is still controversery about the optimal timing of thoracic radiotherapy (TRT). In this study, the outcome of 70 patients who had received TRT at a dose of median 50 Gy (range, 46–60 Gy) with a second or third cycle of chemotherapy (CHT) either concurrently (n=41) or sequentially (n=29) were analyzed retrospectively. All patients were administered a median of five cycles (range, four to six cycles) cisplatin plus etoposide (EP) CHT. Prophylactic cranial radiotherapy was delivered to 30 (43%) patients. The median follow-up for all patients was 15 mo (range, 6–60 mo). The median overall survival was 19 mo in the concurrent arm vs 15 mo in the sequential arm. The 2-yr local control, disease-free survival, and overall survival rates were 60%, 19%, and 36%, respectively. The most common toxicity was esophagitis. However, there were no grade 3–4 esophagitis in either arm. Grade 3–4 hematologic toxicity, on the other hand, appeared significantly more in the concurrent arm (p<0.001). Mid-course of once-daily TRT at a moderate total dose with CHT failed to show any improvement in survival. Additionally, there were no differences between concurrent and sequential CHT with TRT. However, acceptable toxicity rates support the use of once-daily fractionation to higher total dose of TRT.     

Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients

Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with concurrent capecitabine. Median age was 44 years (range: 38–53). The median dose of capecitabine was 1,000 mg/m² twice daily for 14 days (day1–14). Treatment cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per fraction, 5 days per week). Median survival after starting WBRT plus capecitabine was 6.5 months (range 1–34 months). One patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early death. Most commonly reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1. Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1 mucositis (n = 1). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain metastases from breast cancer and need to be further validated in the setting of a clinical trial. An erratum to this article can be found at     

Pulsed Reduced Dose Rate for Reirradiation of Recurrent Breast Cancer

PurposeLocoregionally recurrent breast cancer within a previously irradiated field requires weighing the benefits of reirradiation against the increased rates of toxicity. Here we evaluate the outcomes of patients treated with pulsed reduced dose rate (PRDR) radiation therapy with concurrent low-dose capecitabine as a method to increase the therapeutic ratio of re-treatment.Methods and MaterialsPatients treated from November 2000 to June 1, 2018 with PRDR radiation therapy at University of Wisconsin were identified. Patients were re-treated to a median dose of 54 Gy (range, 37.5-66 Gy) using PRDR radiation therapy, delivering radiation at an apparent dose rate of 6.67 cGy/min to allow for increased sublethal damage repair of normal tissues. The median cumulative dose was 109.8 Gy. Twenty-two patients were treated with concurrent capecitabine, most frequently at 500 mg twice per day. The Kaplan–Meier method was used for survival analysis, and Cox regression analysis was used for univariate and multivariate analysis.ResultsForty-three patients were identified who underwent reirradiation for locoregionally recurrent invasive breast cancer, with a median follow-up of 20.5 months. Twenty-four patients had gross disease. Nineteen patients had simultaneous metastatic disease. The complete response rate was 83.3% in treated patients with gross disease. Locoregional recurrence–free survival was 81.3% and 73.8% for all patients at 1 and 2 years, respectively. Overall survival for patients with localized disease was 95.7% at 1 year and 91.1% at 2 years. The rate of acute grade 3 radiation dermatitis was 25.6% with no other acute grade 3 toxicities. Grade 3 late toxicity occurred in 18.6% of patients.ConclusionsPRDR radiation therapy with capecitabine was a well-tolerated and effective method for treating patients with recurrent breast cancer. Prospective studies are necessary to compare side effects and efficacy with conventional dose rate reirradiation and to evaluate the potential role for capecitabine in the recurrent setting.     

Outcomes of Gamma Knife surgery for craniopharyngiomas

Gamma Knife surgery (GKS) has emerged as a valuable adjuvant treatment modality for recurrent or residual craniopharyngioma. However, prognostic factors pertaining to progression-free survival (PFS) remain poorly understood. A study was conducted to address this issue. A total of 37 consecutive patients undergoing 39 sessions of GKS procedures targeting the solid portions of the tumors at our institution between 1989 and 2005 were analyzed. Twenty-one male and 16 female patients comprised this study. Median age at GKS was 36 years (range, 4–78). Median tumor volume was 1.6 cm³ (range, 0.1–18.6), median marginal dose was 14.5 Gy (range, 6–25), and median maximal dose was 30 Gy (range, 15.6–60). Median follow-up was 50 months (range, 8–212). Univariate and multivariate analyses using Cox proportional hazards model were employed to identify the potential prognostic factors including tumor volume, marginal dose, gender, age at GKS, and status of visual field defect (VFD) in terms of in-field PFS. The actuarial 3- and 5-year in-field PFS were 84.8 and 67.0%, respectively. On univariate analysis, absence of VFD at GKS was a favorable prognostic factor (hazard ratio: 0.279; 95% CI, 0.085–0.913, P = 0.035), whereas on multivariate analysis, absence of VFD at GKS, tumor volume ≤1.6 cm³, and marginal dose >14.5 Gy related to a longer in-field PFS. GKS may offer reasonable control of recurrent or residual craniopharyngiomas. There was a consistent correlation between absence of VFD at the time of GKS and in-field PFS.     

Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery

AimsTo evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery.Materials and methodsIn total, 539 patients with pTis–pT1–pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons.ResultsAt the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (±0.5% standard error) and 2.1% (±0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity.ConclusionThis type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis.     

Phase I/II trial of combination therapy with S-1 and weekly paclitaxel in patients with unresectable or recurrent gastric cancer

Purpose  We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting. Patients and methods  The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m²) was given orally on days 1–21 every 35-day cycle (rest on days 22–35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m², stepping up to 70 mg/m² in 10-mg/m² increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed. Results  The MTD of paclitaxel was estimated to be 60 mg/m², because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m². In the phase II portion, 22 patients were evaluated with 50 mg/m² paclitaxel and 80 mg/m² S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2–75.6%). The median survival time was 283 days (95% CI, 218–508 days). The median number of treatment courses was 4 (range 1–10), indicating that this regimen could be given repeatedly. Conclusions  This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.     

Single and hypofractionated stereotactic radiotherapy with CyberKnife for craniopharyngioma

Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with especially high incidence in Japanese children. Due to the location, proximity and adhesiveness of the tumor to adjacent critical structures, these tumors remain a significant clinical challenge. The purpose of this study was to evaluate the clinical outcome of single and hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients (21 men and 22 women; median age 44 years; range 3–85 years) were treated at two institutions. Three cases were treated in a single fraction to a marginal dose of 13–16 Gy. The other 40 cases were treated in 2–5 fractions to a marginal dose of 13–25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm³ (median 2.0 cm³). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 40 months (range 12–92 months). The 3-year overall survival and local control rates were 100 and 85%, respectively. In-field cyst enlargement was observed in 9 patients. These tumors had significantly larger volumes (mean 6.9 cm³; 95% confidence interval, CI, 2.8–10.9 cm³) than the 34 controlled tumors (2.9 cm³; CI 1.5–4.3 cm³) (P = 0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was observed in only 1 patient. Single and hypofractionated SRT using CyberKnife produced high tumor control rates with minimal complications. Hypofractionated SRT may be useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and for large tumors.     

CT-guided radioactive seed implantation for recurrent rectal carcinoma after multiple therapy

The recurrent carcinoma has been difficult to manage after surgery and radiotherapy, extensive resection of locally recurrent rectal cancer is associated with significant morbidity and mortality. Re-irradiation, even in combination with chemotherapy has shown very short survival. We assess the feasibility and efficacy of CT-guided interstitial permanent brachytherapy with ¹²⁵I or ¹⁰³Pd seeds for recurrent rectal cancer after multiple treatments. Fifteen patients with locally recurrent rectal carcinoma received ¹²⁵I or ¹⁰³Pd seed implants under CT guidance. The minimal peripheral dose of seed implants was 110–165 Gy (median 150 Gy). Two weeks after seed implantation, a 50 Gy of stereotactic radiotherapy was given to one patient; four patients received 2–4 cycles of chemotherapy. A median follow-up was 8 months (range 4–50 months). The duration of pain-free survival was 0–50 months (median 7 months). Local control was maintained for 3–50 months (median 7 months). The 1- and 2-year local controls were 16.2 and 8.1%, respectively. Eleven patients died: two (18.2%) of local recurrence, seven (63.6%) of local recurrence and metastases, and two (18.2%) of metastases. Four patients (26.7%) survived the median survival was 9 months. The 1- and 2-year actuarial overall survival rates were 42.9% and 10.7%, respectively. One patient (7.6%) experienced a grade 4 toxic event; there was no associated neuropathy. CT-guided radioactive seed implantation is feasible and safe as a salvage or palliative pain relief treatment for patients with recurrent rectal cancers after surgery and radiotherapy.     

The association between biological subtype and locoregional recurrence in newly diagnosed breast cancer

We investigated the association between the risk of locoregional recurrence (LRR) and biological subtypes defined by hormonal receptors (HR) and HER-2 status in women with invasive breast cancer (BC). A total of 618 newly diagnosed BC patients were identified from a cancer registry within a single institution with standardized methods of tumor assessment for estrogen receptor (ER), progesterone receptor (PR), and HER-2. Patients were stratified based on surgical treatment, breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well as biological subtypes: HR+/HER-2− (ER-positive or PR-positive, HER-2-negative), HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR−/HER-2+ (ER-negative and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2-negative). The association between clinicopathological factors, biological subtype and LRR was evaluated with univariate and multivariate Cox analysis. With a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate analysis, TN, tumor size ≥2 cm and lymph node (LN) positivity were associated with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively). In BCT group, HR−/HER-2+ and LN positivity were associated with increased risk of LRR (HR 11.13; 95% CI 2.78–44.53; P = 0.0007 and HR 5.40; 95% CI 1.67–17.43; P = 0.0048, respectively). In MRM group, TN subtype and LN positivity were associated with increased risk of LRR (HR 4.72; 95% CI 1.53–14.52; P = 0.0069 and HR 3.23; 95% CI 1.44–7.29; P = 0.0047, respectively). Compared to HR+/HER-2−, HR−/HER-2+ treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER, PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of LRR based on surgical treatment. Our findings suggest a different follow-up and locoregional treatment for patients with HR−/HER-2+ and TN subtypes.     

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

Abstract  

The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991–7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m² and cisplatin 25 mg/m² on day 1, followed by 5-FU 180 mg/m²/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week’s rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40–78 years). The median number of cycles per patient was 4 (range 2–6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16–51], a median time to progression of 6.4 months (95% CI 5.4–7.4), and a median overall survival of 10.7 months (95% CI 6.6–14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III–IV toxicities observed in >5% of patients were anemia and mucositis.     

Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation

BACKGROUND:

The objective of this study was to identify predictors of locoregional recurrence (LRR) after neoadjuvant therapy (NAT) and postmastectomy radiation (PMRT) in a cohort of patients with stage II through III breast cancer and to determine whether omission of the supraclavicular field had an impact on the risk of LRR.

METHODS:

The authors reviewed records from 464 patients who received NAT and PMRT from January 1999 to December 2009.

RESULTS:

The median patient age was 50 years (range, 25‐81 years). Clinical disease stage was stage II in 29% of patients, stage III in 71%, and inflammatory in 14%. Receptor status was estrogen receptor (ER)‐positive in 54% of patients, progesterone receptor (PR)‐positive in 39%, human epidermal growth factor receptor 2 (HER2)‐positive in 24%, and negative for all 3 receptors (triple negative) in 32%. All patients received NAT and underwent mastectomy, and 19.6% had a complete pathologic response in the breast and axilla, 17.5% received radiation to the chest wall only, and 82.5% received radiation to the chest wall and the supraclavicular field; omission of the supraclavicular field was more common in patients with lower clinical and pathologic lymph node status. The median follow‐up was 50.5 months, and the 5‐year cumulative incidence of LRR was 6% (95% confidence interval, 3.9%‐8.6%). Predictors of LRR were clinical stage III (P = .038), higher clinical lymph node status (P = .025), higher pathologic lymph node status (P = .003), the combination of clinically and pathologically positive lymph nodes (P < .001), inflammatory presentation (P = .037), negative ER status (P = .006), negative PR status (P = .015), triple‐negative status (P < .001), and pathologic tumor size >2 cm (P = .045). On univariate analysis, omission of the supraclavicular field was not associated significantly with LRR (hazard ratio, 0.89; P = .833); however, on multivariate analyses, omission of the supraclavicular field was associated significantly with LRR (hazard ratio, 3.39; P = .024).

CONCLUSIONS:

Presenting stage, receptor status, pathologic response to neoadjuvant therapy, and omission the supraclavicular field were identified as risk factors for LRR after neoadjuvant therapy and PMRT. Cancer 2013. © 2012 American Cancer Society.     

A phase II study of oxaliplatin in combination with doxorubicin as first-line systemic chemotherapy in patients with inoperable hepatocellular carcinoma

Purpose  We designed a phase II trial of the combination with oxaliplatin and doxorubicin for patients with unresectable HCC to evaluate the overall response rate (ORR) and the toxicity. Methods  Forty patients with inoperable, systemic chemotherapy naive HCC were enrolled. Finally, 32 patients received oxaliplatin (130 mg/m²) and doxorubicin (60 mg/m²) every 3 weeks. Results  Eighty-two treatment cycles were administered (median 2 cycles, range 1–6). There was no treatment-related mortality. The ORR was 15.6% (95% CI, 3.3–28.7) with five partial responses. The median overall survival and median overall progression free survival were 31 weeks (95% CI, 22–40 weeks) and 12 weeks (95% CI, 5-19 weeks). Nausea and peripheral neuropathy were most frequent non-hematologic toxicities (nausea, n = 15; peripheral neuropathy, n = 10). The most frequent grade 3–4 hematologic adverse event was neutropenia (14 of 82 cycles) including three cases of febrile neutropenia. Conclusions  The combination of oxaliplatin and doxorubicin showed modest activity and a tolerable toxicity profile in advanced HCC patients.