H. Ren

Spontaneous Regression of Thoracic Metastases While Progression of Brain Metastases After Stereotactic Radiosurgery and Stereotactic Body Radiotherapy for Metastatic Renal Cell Carcinoma: Abscopal Effect Prevented by the Blood-Brain Barrier?

Department of Radiation Oncology, The Methodist Hospital, Research Institute, ouston, TX Department of Radiation Oncology, The Methodist Hospital, Houston, TX Department of Radiology and Radiation Oncology, Kitasato University School of edicine, Sagamihara, Kanagawa, Japan Department of Radiation Oncology, Cancer Hospital (Institute), Chinese Academy f Medical Sciences, Peking Union Medical College, Beijing, China Department of Radiology, The Methodist Hospital, Houston, TX Medical Branch, The University of Texas, Houston, TX Division of Oncology, The University of Texas, Health Science Center, Memorial ermann Cancer Center, Houston, TX

Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients.

PURPOSE To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. METHODS AND MATERIALS Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. RESULTS A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. CONCLUSIONS According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer

Preoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group. Therefore, miR-345 was selected as a candidate for further analysis. We assessed the correlation between the miRNA signatures and the chemoradiotherapeutic response in 20 randomly selected LARC tissue samples (Validation set) and 87 serum samples (Training set) by qRT-PCR. Further, we validated the results in 42 randomly selected LARC serum samples (Validation set). High miR-345 expression was significantly correlated with unfavorable pre-CRT pathological response in tissue and serum. Moreover, low miR-345 levels predicted superior 3-year local recurrence free survival (LRFS). Taken together, circulating serum miR-345 correlates with unfavorable pre-CRT response and poor locoregional control in LARC. It might be a promising biomarker to facilitate patient stratification for personalized treatment.

Phase I study of postoperative radiotherapy combined with capecitabine for gastric cancer

AIM To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer. METHODS We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins (R0) or microscopic (R1) or macroscopic (R2) resection. Intensity modulated radiotherapy (IMRT) using a five-to-seven-field, coplanar, sliding window technique was delivered to the tumor bed (T4b), anastomosis site, duodenal stump and regional lymph nodes (LNs) to a total dose of 45 Gy (1.8 Gy/fraction, 5 d/wk). Patients with R1 or R2 resection received 10.8 Gy as a boost. Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m²) of 625 (level I, n = 6), 700 (level II, n = 6), 800 (level III, n = 6), 900 (level IV, n = 0) and 1000 (level V, n = 0). DLT was defined as grade 4 leukopenia or neutropenia, grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity. RESULTS Between October 2007 and August 2009, 18 patients (12 men, 6 women; median age, 54 years) were enrolled in the study. The median number of positive LNs was 6, and total number of resected LNs was 19. Twelve patients underwent R0 resection (66.7%). Fifteen patients received adjuvant chemotherapy under the leucovorin, fluorouracil and oxaliplatin (FOLFOX4) regimen. Six patients each were enrolled at dose levels I, II and III. Grade 1-3 leukopenia (16 patients, 88.9%), anorexia (15, 83.3%) and nausea (15, 83.3%) were the most common toxicities. Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-I patient. Grade 3 anorexia and nausea occurred in one level-II patient. One level-III patient developed grade 4 neutropenia, while another developed grade 3 radiation esophagitis. No abnormal liver or renal function examinations were observed. Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts (total dose, 55.8 Gy). CONCLUSION The MTD of capecitabine was 800 mg/m² twice daily concurrent with IMRT for gastric cancer after surgery. The DLTs were anorexia/nausea, vomiting, neutropenia and radiation esophagitis.

Survival benefit with IMRT following narrow‐margin hepatectomy in patients with hepatocellular carcinoma close to major vessels

To investigate the role of post‐operative intensity‐modulated radiotherapy (IMRT) in patients receiving narrow‐margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels.

Intensity-modulated radiotherapy following null-margin resection is associated with improved survival in the treatment of intrahepatic cholangiocarcinoma

BACKGROUND The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. METHODS Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. CONCLUSIONS The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.

Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer

Background The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer. Patients We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m2/day), administered twice daily from day 1–14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy. Results The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%). Conclusions This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.

Patterns of Primary Tumor Invasion and Regional Lymph Node Spread Based on Magnetic Resonance Imaging in Early-Stage Nasal NK/T-cell Lymphoma: Implications for Clinical Target Volume Definition and Prognostic Significance

PURPOSE This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma (NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns. METHODS AND MATERIALS A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy. RESULTS The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surrounding the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS. CONCLUSIONS Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3–4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

a Phase ii prospective nonrandomized trial of magnetic resonance imaging-guided hematopoietic bone marrow-sparing radiotherapy for gastric cancer patients with concurrent chemotherapy

Purpose This study aimed to spare hematopoietical bone marrow (BM) identified by magnetic resonance (MR) radiation in order to alleviate acute hematologic toxicity (HT) for gastric cancer patients treated with postoperative chemoradiotherapy (CRT). Methods A prospective, open-label, single-arm Phase II study (Clinicaltrials.gov; NCT 01863420) was conducted in 25 patients with gastric cancer who were eligible for postoperative concurrent CRT. The MR images of vertebral body T8-L4 were fused with images of simulating computed tomography. Hematopoietical BM was contoured according to the MR and spared in radiotherapy plan. The CRT regimen consisted of daily capecitabine (1600 mg/m2/d) and 45 Gy of radiation at 1.8 Gy per day. Primary endpoints were grade ≥3 HT that occurred within 2 months of initiation of CRT. The relationship between HT and dose–volume of BM was estimated by multivariable linear regression model. Results Twenty four patients (96%) had T3–4 disease and 22 (88%) had disease with node positive. The median age was 53 years (range, 28–73 years). Before concurrent CRT, adjuvant chemotherapy was administered with a mean cycle of 4.3±0.5. Only five patients (20%) developed grade 3–4 HT during treatment, among whom two (8.0%) patients experienced grade 3–4 leucopenia, two (8.0%) experienced neutropenia, and two (8.0%) experienced thrombocytopenia, respectively. None of the patients showed grade 3–4 anemia. Multivariable linear regression revealed increased BM-V5 (P=0.03) and BM-V20 (P=0.002) were found to be significantly associated with decreased white blood cells nadirs in multivariable regression; increased BM-V20 (P<0.001) with decreased absolute neutrophil count nadirs, increased BM-V30 (P=0.002) and volume of BM (P=0.001) with decreased platelet count nadirs. Conclusion Irradiation of active BM identified by MR is associated with HTs. Techniques to limit low-dose radiation, especially V20, to BM could reduce HT in gastric cancer patients.