Yuan Tang

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

PURPOSEnThis 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.nnnMETHODS AND MATERIALSnA 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnEarly-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.

Phase III randomized trial of preoperative concurrent chemoradiotherapy versus preoperative radiotherapy for patients with locally advanced head and neck squamous cell carcinoma

Purpose To determine the role of preoperative concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). Methods A total of 222 patients with stage III/IVA-B HNSCC were randomly assigned to receive preoperative concurrent chemoradiotherapy (Pre-S CRT, weekly cisplatin 30mg/m2) or preoperative radiotherapy alone (Pre-S RT). Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Results With a medial follow-up of 59 month, the 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) of Pre-S CRT v Pre-S RT group were 53.8% v 39.0% (hazard ratio [HR], 0.74, 95% CI, 0.50 to 1.10, P = 0.13), 53.2% v 38.7%, (HR, 0.69, 95% CI, 0.47 to 1.01, P =0.06), and 80.4% v 68.1% (HR, 0.53, 95% CI, 0.28 to 0.98, P = 0.04), respectively. In patients with larynx-hypopharynx primaries, the 5-year OS, PFS and DMFS of Pre-S CRT v Pre-S RT were 62.7% v 38.8% (HR, 0.59, 95% CI 0.35 to 1.02, P = 0.054), 63.1% v 39.9% (HR, 0.52; 95% CI 0.30 to 0.89, P = 0.03) and 86.2% v 63.3% (HR, 0.35, 95% CI 0.15 to 0.82, P = 0.01), respectively. Conclusion The addition of weekly cisplatin concurrent to preoperative RT does not improve OS, but improve DMFS in locally advanced HNSCC. However, in a subset of patients with the larynx-hypopharynx primaries, preoperative chemoradiotherapy has significantly improved PFS and DMFS, and has also provided a borderline benefit in OS in comparison with preoperative radiotherapy alone.

Tomotherapy as an adjuvant treatment for gastroesophageal junction and stomach cancer may reduce bowel and bone marrow toxicity compared to intensity-modulated radiotherapy and volumetric-modulated arc therapy

Purpose To compare dosimetric parameters of intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and tomotherapy (TOMO) in the adjuvant treatment of gastroesophageal junction (GEJ)/stomach cancer. The planning goal was to maintain high target coverage while keeping the dose to the bowel and bone marrow (BM) as low as possible. Materials and Methods After curative surgery, 16 patients with GEJ/stomach cancer were re-planned by coplanar IMRT (five fixed beam), VMAT (double-arc), and TOMO. The dose to the planning target volume (PTV) was 45 Gy in 25 fractions. The target parameters, including the homogeneity index (HI) and conformity index (CI), and doses to the organs at risk (OARs) were analyzed. Results Dosimetric parameters for PTV and OARs were comparable among the three techniques. However, TOMO provided improved conformity (CI = 0.92±0.03) and homogeneity (HI = 1.07±0.02) than IMRT (CI = 0.87±0.03; HI = 1.09±0.02; p < 0.05) and VMAT (CI = 0.86±0.03; HI = 1.09±0.02; p < 0.01). TOMO also improved dose sparing of the bowel (percentage of the volume receiving a dose of ≥ 30 Gy [V30] = 23.24±9.85) and BM (V30 = 71.66±6.15) compared with IMRT (bowel V30 = 30.02±11.74; BM V30 = 83.74±8.42; p < 0.01) and VMAT (bowel V30 = 31.88±11.59; BM V30 = 79.51±9.07; p < 0.01). Conclusions TOMO is a good option for adjuvant treatment of GEJ/stomach cancer in patients undergoing radical surgery due to its superior bowel and BM dose sparing, dose conformity and dose homogeneity; however, future studies are required to validate its clinical efficacy.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

PURPOSEnTo assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL).nnnMETHODS AND MATERIALSnSixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (Dmean) to the parotid glands on xerostomia.nnnRESULTSnThe median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9xa0Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The Dmean to the parotid glands had a linear correlation with late grade ≥2 xerostomia.nnnCONCLUSIONSnIMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24xa0Gy for early-stage WR-DLBCL.

LncRNA and mRNA signatures associated with neoadjuvant chemoradiotherapy downstaging effects in rectal cancer: LI et al.

Radiotherapy plays a crucial role in combined treatment modality in local advanced rectal cancer (LARC). While neoadjuvant chemoradiotherapy responses were variable in LARC patients, so, it is important to identify genes that closely associated with short‐term and long‐term responses to radiotherapy. In this study, we profiled long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression values of LARC patients with different neoadjuvant chemoradiotherapy downstaging depth score based on Agilent Arraystar Human LncRNA V3.0 Array(Agilent, CA). LncRNAs and mRNAs with aberrant expression values between the two groups of LARC patients were identified and lncRNA‐miRNA‐mRNA regulation network was also obtained through the combination of miRcode and miRTarBase database. Gene interaction network and module analysis of differential expression mRNAs contained in the lncRNA‐miRNA‐mRNA network identified five hub genes, including KRAS, PDPK1, PPP2R5C, PPP2R1B, and YES1, that should be closely associated with LARC’s response to chemoradiotherapy. Besides, Kaplan‐Meier analysis based on the Cyber Research Center (CRC) data set from The Cancer Genome Atlas indicated that aberrant expression of the five hub genes is significantly associated with CRC overall survival. In conclusion, we obtained several biomarkers that should be associated with neoadjuvant chemoradiotherapy response in LARC, which should be helpful for individual treatment and prognosis improvement.

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypI stage after neoadjuvant chemo-radiotherapy versus de novo stage pI cohort: A propensity score-matched analysis

ObjectivenPrognosis of patients with locally advanced rectal cancer (LARC) but achieving ypT1-2N0 stage after neoadjuvant concurrent chemo-radiotherapy (CRT) has been shown to be favorable. This study aims to determine whether the long-term outcome of ypT1-2N0 cases can be comparable to that of pT1-2N0 cohort that received definitive surgery for early disease.nnnMethodnFrom January 2008 to December 2013, 449 consecutive patients with rectal cancer were treated and their outcome maintained in a database. Patients with LARC underwent total mesorectal excision (TME) surgery at 4-8 weeks after completion of CRT, and those achieving stage ypI were identified as a group. As a comparison, stage pI group pertains to patients whose initially limited disease was not upstaged after TME surgery alone. After propensity score matching (PSM), comparisons of local regional control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were performed using Kaplan-Meier analysis and log-rank test between ypI and pI groups. Down-staging depth score (DDS), a novel method of evaluating CRT response, was used for subset analysis.nnnResultsnOf the 449 patients, 168 matched cases were generated for analysis. Five-year LC, DMFS, DFS and OS for stage pI vs. ypI groups were 96.7% vs. 96.4% (P=0.796), 92.7% vs. 73.6% (P=0.025), 91.2% vs. 73.6% (P=0.080) and 93.1% vs. 72.3% (P=0.040), respectively. In the DDS-favorable subset of the ypI group, LC, DMFS, DFS and OS resulted in no significant differences in comparison with the pI group (P=0.384, 0.368, 0.277 and 0.458, respectively).nnnConclusionsnLC was comparable in both groups; however, distant metastasis developed more frequently in down-staged LARC than de novo early stage cases, reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response. DDS can be an indicator to identify a subset of the ypI group whose long-term oncologic outcomes are as good as those of stage pI cohort.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate

BackgroundIn this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.MethodsIn the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (nu2009=u200971), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (nu2009=u200943), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45–50.4xa0Gy in 25–28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600xa0mg/m2) on days 1–14 and 22–35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.ResultsBetween June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (pu2009=u20090.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, pu2009=u20090.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137–0.868, pu2009=u20090.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143–0.938, pu2009=u20090.036).ConclusionsIn pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.