Local-regional Recurrence-free Survival Research Articles

Influence of radiotherapy interruption on esophageal cancer with intensity-modulated radiotherapy: a retrospective study

BackgroundRadiotherapy interruption (RTI) prolongs the overall total treatment time and leads to local control loss in many cancers, but it is unclear in esophageal cancer. We aimed to evaluate the influence of RTI on the overall survival (OS), progression-free survival (PFS), and local-regional recurrence-free survival (LRFS) of patients with esophageal cancer undergoing chemoradiotherapy.MethodsA total of 299 patients with esophageal squamous cell carcinoma from 2017 to 2019 were retrospectively analyzed to investigate the effect of RTI on OS, PFS, and LRFS. The delayed time of radiotherapy interruption was calculated as the actual radiation treatment time minus the scheduled time. The univariate and multivariate analyses were performed by the COX proportional hazards regression models, and the survival analysis was performed through the Kaplan‒Meier method, and compared with the log-rank test.ResultsThe 3-year OS, PFS, and LRFS rates were 53.0%, 42.0%, and 48.0%, respectively. The univariate and multivariate analyses showed that the delayed time > 3 days was an independent adverse prognostic factor for OS (HR = 1.68, 95% CI 1.10–2.55, p = 0.016), and LRFS (HR = 1.74, 95% CI 1.18–2.57, p = 0.006). The patient with a delayed time of > 3 days had poorer survival rates of OS, and LRFS than patients with a delayed time of ≤ 3 days (OS, p = 0.047; LRFS, p = 0.013), and the survival outcomes of patients with shorter delayed time (1–3 days) were slightly different from the patients without interruptions. The impact of delay time on PFS is not statistically significant, but the survival outcomes of the two groups were slightly different.ConclusionThere was a significant correlation between delayed time and local control of esophageal cancer. The delayed time for more than 3 days might decrease the survival outcome, and increase the local recurrence risk.

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

IntroductionMetronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy.AimWe aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC.Subjects and methods28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups.ResultsThe median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05 ).ConclusionMetronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC.Trial registrationNCT02958111, date of registration 04-11-2016.

Combined pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts survival and prognosis in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study

The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy

PurposeThe effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and MethodsWe retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. ResultsThe median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. ConclusionLong-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.

De-escalated radiotherapy for HER2-overexpressing breast cancer patients with 1-3 positive lymph nodes undergoing anti-HER2 targeted therapy.

In the era of anti-HER2 targeted therapy, the potential clinical feasibility of considering HER2-overexpressing breast cancer cases presenting with 1-3 positive axillary lymph nodes as low-risk, and thereby contemplating postoperative radiotherapy reduction, remains an important subject for in-depth examination. The aim of this retrospective study was to evaluate the effectiveness of de-escalated radiotherapy in T1-2N1M0 HER2-overexpressing breast cancer patients receiving anti-HER2 targeted therapy. Specifically, omitting regional lymph node irradiation (RNI) after breast-conserving surgery and only performing whole-breast irradiation or omitting postmastectomy radiation therapy. A retrospective analysis was conducted on 429 patients with stage T1-2N1M0 primary invasive HER2-overexpressing breast cancer from our center between 2004 and 2018. Patients who received anti-HER2 targeted therapy were divided into an RNI group and a no RNI group to assess the role of RNI. The prognostic role of RNI was investigated via the Kaplan-Meier method and Cox proportional hazards modeling. The median follow-up time was 46.8 months (range 7.1-225.8 months). In the anti-HER2 targeted therapy group RNI yielded no significant improvements in invasive disease-free survival (IDFS) (p = 0.940), local-regional recurrence-free survival (p = 0.380), distant metastases-free survival (p = 0.698), or overall survival (p = 0.403). Estrogen receptor (ER) status (hazard ratio [HR] 0.105, 95% confidence interval [CI] 0.023-0.749, p = 0.004) and lymph vascular invasion status (LVI) (HR 5.721, 95% CI 1.586-20.633, p = 0.008) were identified as independent prognostic factors for IDFS, and ER-positive and LVI-negative patients exhibited better prognoses. Omitting RNI may be a safe option in T1-2N1 HER2-overexpressing breast cancer patients receiving standardized anti-HER2 targeted therapy; particularly in ER-positive or LVI-negative subgroups.

Perineural Invasion Is a Significant Prognostic Factor in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

(1) Objectives: This systematic review and meta-analysis aimed to summarize current evidence regarding the prognostic role of perineural invasion (PNI) in patients with oral squamous cell carcinoma (OSCC). (2) Methods: We searched Cochrane Central, ProQuest, PubMed, Scopus, Science Direct, and Web of Science, using relevant keywords to identify eligible articles. Two independent reviewers conducted two-stage screening, data extraction, and quality assessment. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) criteria. All analyses were performed using comprehensive meta-analysis (CMA; version 3.3.070) software. (3) Results: The study included 101 published articles encompassing 26,062 patients. The pooled analyses showed that PNI was associated with significantly worse overall survival (OS; HR = 1.45, 95% CI: 1.32-1.58; p < 0.001), worse disease-specific survival (DSS; HR = 1.87, 95% CI: 1.65-2.12; p < 0.001), and worse disease-free survival (DFS; HR = 1.87, 95% CI: 1.65-2.12; p < 0.001). Similarly, both local recurrence-free survival (LRFS) and regional recurrence-free survival (RRFS) were worse in patients with PNI (HR = 2.31, 95% CI: 1.72-3.10, p < 0.001; and HR = 2.04, 95% CI: 1.51-2.74, p < 0.001), respectively. The random-effect estimate of three studies demonstrated that the presence of PNI was associated with worse failure-free survival (FFS; HR = 2.59, 95% CI: 1.12-5.98, p < 0.001). (4) Conclusions: The current evidence suggests that PNI can be used as an independent predictor of the prognosis for patients with OSCC. The presence of PNI was associated with worse OS, DFS, DSS, FFS, and with recurrence. Asian patients and patients with extra-tumoral or peripheral PNI invasion were associated with worse prognosis.

Survival Outcomes and Factors Affecting Prognosis in Patients with Head and Neck Region Mucoepidermoid Carcinoma Treated with Adjuvant Radiotherapy

Aim: This study aims to ascertain the clinical and pathological factors linked to the outcomes of patients subjected to surgical intervention and postoperative radiotherapy for mucoepidermoid carcinoma (MEC) originating from both major and minor salivary glands in the head and neck region.&#x0D; Material and Method: In this retrospective review, medical records of 42 patients who underwent surgery and subsequent radiotherapy for localized MEC in the major and minor salivary glands of the head and neck were analyzed to identify clinicopathological determinants of overall survival. Secondary endpoints encompassed local-regional control, distant metastasis-free survival, and disease-free survival.&#x0D; Results: The median age of the patient cohort was 56 years, comprising 52.4% males and 47.6% females. The median follow-up period spanned 36 months, with a range of 6 to 88 months. All patients underwent curative surgery, followed by adjuvant radiotherapy. The 2-year and 5-year rates for overall survival (OS), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 92% and 72.6%, 92.2% and 85.6%, 84.8% and 73%, 82% and 67.3%, respectively. Notably, only histologic grade emerged as a statistically significant prognostic factor, influencing both OS (p=0.019), DMFS (p=0.014), and DFS (p=0.044).&#x0D; Conclusion: The histologic grade of the tumor is the foremost determinant impacting the outcomes of MEC cases. Adjuvant radiotherapy is recommended for high-grade tumors, while its application for low-grade and intermediate-grade tumors should be individualized based on the anticipated risk of recurrence. This underscores the significance of tailoring treatment approaches according to histologic characteristics.

Mismatch Repair Status is an Effective Prognostic Factor for Early-Stage Endometrial Carcinoma

This study is to evaluate the impact of mismatch repair (MMR) status on prognosis among patients with stage I to II (FIGO 2009) endometrial carcinoma (EC) treated with hysterectomy and adjuvant RT. Between Oct. 2017 and Dec. 2020, patients with stage I to II (FIGO 2009) EC who had undergone hysterectomy followed by adjuvant RT in our institution were retrospectively reviewed. Clinical characteristics were compared between patients with proficient and deficient mismatch repair (pMMR and dMMR) using Pearson Chi-Square test for categorical variables. Kaplan-Meier method and log-rank test were used to compared overall survival (OS), disease-free survival (DFS), local-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Statistically significant difference was set as p<0.05. Totally 276 stage I to II EC patients with known MMR status were included in this study. Among them, 211 patients were classified as pMMR while 65 patients were classified as dMMR. When compared to pMMR, patients with dMMR were more likely to have grade 3 and non-endometrioid type(37.8% vs. 20.8%, p = 0.014), lympho-vascular invasion (36.7% vs. 16.3%, p = 0.000), young age (<60) (28.6% vs. 17.2%, p = 0.027), HIR to HR classification(30.9% vs. 16.1%, p = 0.004). Of all the 276 patients, the median follow-up time was 31 months. Two-year DMFS was superior for pMMR compared to dMMR patients (96.3% vs. 95.0%, p = 0.048). Two-year DFS tended to be better for pMMR than dMMR patients with survival curves not crossed over each other (93.0% vs. 86.8%, p = 0.074). Two-year OS (98.9% vs. 98.4%, p = 0.716) and LRFS (96.3% vs. 95.0%, p = 0.815) were not different between pMMR/dMMR patients. For HIR to HR group, we reached the similar conclusion while for LR to IR group, survival statistics were not different between pMMR/dMMR patients. As to failure pattern, dMMR were more likely to have distant failure while local and regional failure were not different between the two groups. For stage I to II EC, patients with dMMR have poorer DMFS and DFS compared to pMMR patients especially in HIR to HR risk classification. The combination of MMR status and other clinical and pathological factors may establish a new prognostic model and form a new risk stratification system.

T4 larinks kanseri için tedavi seçimi: kemoradyoterapi ile organ koruyucu yaklaşım mümkün mü yoksa multimodalite tedavi daha mı etkili?

Aims: Organ-preserving approach is recommended as an evidence-based treatment option for advanced laryngeal cancer (LC) with similar survival results. However, the organ-preserving approach in T4 disease is controversial, and surgical treatment is primarily preferred. Today, chemoradiotherapy (CRT) is applied to T4 LC patients who are inoperable for medical or surgical reasons and upon the request of the patient who refuses the recommended surgical treatment. The aim of this study was to evaluate the treatment outcomes in patients with T4 LC who underwent CRT for these conditions and received adjuvant radiotherapy (RT)/CRT as the standard treatment regimen after surgery.&#x0D; Methods: A retrospective review of T4 LC patients treated with CRT (17 patients) and adjuvant RT/CRT (26 patients) between 2015 and 2021 was conducted. Overall survival (OS), local regional recurrence-free survival (LRRFS), and disease-free survival (DFS) were compared between the groups. The organ preservation rate was determined for the CRT group.&#x0D; Results: The median follow-up time for the entire cohort was 41 months, the 5-y OS, LRRFS, and DFS were 55.9%, 51.4%, and 51.9%, respectively. Statistically significant difference was found between the treatment groups in terms of 5-y OS, LRRFS, and DFS rates, and survival was found to be decreased in the CRT group (35.3% vs. 70.2%, p=0.007; 22.1% vs. 75.1%, p= 0.001; 22.1% vs. 75.7%, p=0.001). With respect to other clinicopathological factors, age was the only significant factor in on OS in multivariate analysis, whereas tumor size, nodal stage, and ECE (in the postoperative RT group, except LRRFS) were linked with OS, LRRFS, and DFS rates. Among the patients who underwent CRT, OS was found to be better in the group applied due to the patient’s request compared to the patients referred for RT due to medical or surgical inoperability, and in multivariate analysis, the indication for RT remained an independent predictor of OS. In addition, the 3-y organ preservation rate was 81.5% in the CRT group.&#x0D; Conclusion: The surgical arm had statistically significantly superior results in terms of OS, LRRFS, DFS compared to the CRT group. However, it is also noteworthy that OS was better in cases where RT is applied at the patient’s request without inoperable disease. In addition, laryngeal protection was observed to a large extent in the CRT arm.

Effect of tumor-infiltrating lymphocytes depending on the presence of postmastectomy radiotherapy on the prognosis in pT1-2N1M0 breast cancer.

Currently, it remains unclear regarding the association between tumor-infiltrating lymphocytes (TILs) and the efficacy of postoperative radiotherapy in primary tumors. Here we attempted to investigate the effect of TILs depending on the presence of postmastectomy radiotherapy (PMRT) on the prognosis in pT1-2N1M0 breast cancer. The clinical data of pT1-2N1M0 breast cancer patients undergoing mastectomy and axillary lymph node dissection were retrospectively analyzed. The effect of TILs on the prognosis was assessed based on the infiltration degree (low: TILs ≤10%, high: TILs >10%), and then the prognosis of patients with low and high infiltration of TILs was analyzed based on presence or absence of PMRT. Totally 213 patients were eligible for the study, including 162 cases of low infiltration and 51 of high infiltration. High-infiltration patients tended to be ER/PR-negative, HER2-positive, and have high histological grade. The infiltration in triple-negative and HER2-positive subtypes was higher compared with Luminal A subtype. Regarding local-regional recurrence-free survival, recurrence-free survival, and overall survival (OS) rates, the differences were all inapparent whether in high- and low-infiltration patients or in high-infiltration patients with/without PMRT. Compared with those without PMRT, low-infiltration patients with PMRT showed a significantly increased OS rate (92.8% vs. 80.0%, p=0.023). Multivariate analysis further confirmed PMRT as an independent predicator of OS in low-infiltration patients (HR: 0.228, 95%CI: 0.081-0.644, p=0.005). High infiltration of TILs in pT1-2N1M0 breast cancer may be associated with clinicopathological factors. Low-infiltration patients, but not high-infiltration patients, may derive survival benefits from PMRT.

The association of anemia and high neutrophil-lymphocyte ratio with decreased survival in patients with laryngeal cancer treated with radiotherapy

Aims: We aimed to examine the prognostic value of inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and anemia on oncological outcomes in patients with laryngeal squamous cell carcinomas (LSCC) treated with radiotherapy.&#x0D; Methods: 213 LSCC patients analyzed retrospectively. Inflammatory markers were established by examining blood samples taken within 7 days before treatment. Patients were categorized into two groups: low and high according to NLR, PLR, and SII threshold values. In addition, to evaluate the effect of hemoglobin (Hb) level, the threshold value of each inflammatory marker and Hb level were combined, and 3 groups were formed (3 groups for NLR, 3 groups for PLR, and 3 groups for SII). The relationship between inflammatory markers and overall survival (OS), disease-free survival (DFS), and local regional recurrence-free survival (LRRFS) was investigated.&#x0D; Results: In univariate analysis, high NLR, PLR, SII, and low Hb (

Salvage stereotactic reirradiation for intraprostatic cancer recurrence: A large retrospective study

Prostate cancer is the most common cancer in men. Thirty to forty-seven percent of patients treated with exclusive radiotherapy for prostate cancer will experience intraprostate recurrence. The use of radiotherapy in stereotactic conditions allows millimetric accuracy in irradiation to the target zone that minimizes the dose to organs at risk. In this study, we evaluated the clinical outcome of prostatic reirradiation with stereotactic body radiation therapy (SBRT) in patients with intraprostatic recurrence initially treated by radiotherapy. This single-center retrospective study included 41 patients diagnosed with exclusive local recurrence of prostate cancer after radiotherapy and treatedby stereotactic Cyberknife irradiation. The objective of this study was to assess the efficacy and the safety of stereotactic reirradiation for patients with intraprostatic recurrence initially treated with radiotherapy. Median follow-up was 35 months. The 2-year biochemical relapse-free survival was 72.89%, the 2-year local recurrence free survival was 93.59%, the 2-year local regional recurrence-free survival was 85.24%, and the 2-year metastasis-free survival was to 91.49%. The analysis of toxicities showed a good tolerance of stereotactic irradiation. Urinary and gastro-intestinal adverse events was mostly of grades 1-2 (CTCAEv4). Grade 3 toxicity occurred in one to two patients. Stereotactic reirradiation appears effective and well-tolerated for local recurrence of prostate cancer and might allow to delay the introduction of hormonal therapy and its side effects.

Extensive clinical target volume in postoperative chemoradiotherapy for esophageal squamous cell carcinoma: a phase II clinical trial (ESO-Shanghai 9)

BackgroundTo compare the efficacy and safety of postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy with radiotherapy only for the postoperative treatment of esophageal squamous cell carcinoma.MethodsThis trial was a single-arm phase II trial. Patients who underwent a radical transthoracic resection with negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4N0M0 or pTxN + M0, AJCC 7th) were eligible for this study. Postoperative radiotherapy was performed at a total dose of 45 Gy in 25 fractions with clinical target volumes of the tumor bed, anastomosis, bilateral supraclavicular, mediastinal, left gastric and celiac trunk lymph node areas. Five cycles of weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) were given as concurrent chemotherapy. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival, disease free survival, local-regional recurrence free survival, distant metastasis free survival and adverse events. All endpoints were compared with those in ESO-Shanghai 8 study with postoperative radiotherapy alone (40 Gy/20Fx).ResultsA total of 70 patients were enrolled from 2016 to 2018. The 2-year local control rate was 87.9% (95% CI: 83.3–92.3) in this study, which achieved the hypothesized 2-year local control rate of at least 83%. Overall survival, disease free survival, local-regional recurrence free survival and distant metastasis free survival in this study were also longer than those in previous ESO-Shanghai 8 study while most toxicities were increased and two patients in this study died of radiation pneumonitis.ConclusionsPostoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy was effective. Treatment related toxicity was increased due to higher treatment intensity.Trial registration clinicaltrials.gov: NCT02916511.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Effect of Adjuvant Radiation Dose on Survival in Patients with Esophageal Squamous Cell Carcinoma.

Background: For patients with esophageal squamous cell carcinoma (ESCC) treated with surgery alone, the incidence of local-regional recurrence remains unfavorable. Postoperative radiotherapy (PORT) has been associated with increased local-regional recurrence-free survival (LRFS), although its application is limited by concerns of PORT-related toxicities. Methods: Among 3591 patients with ESCC analyzed in this study, 2765 patients with T3-4N0 and T1-4N1-3 lesions and specific local-regional status information were analyzed in a subsequent analysis of adjuvant radiation dose (aRTD) effect. Application of the restricted cubic spline regression model revealed a non-linear relationship between aRTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRFS and overall survival (OS)/ disease-free survival (DFS). Results: For patients staged T1−2N0, T1−2N1−3, T3−4N0, and T3−4N1−3, 5-year OS in PORT and non-PORT groups were 77.38% vs. 72.91%, p = 0.919, 52.35% vs. 46.60%, p = 0.032, 73.41% vs. 61.19%, p = 0.005 and 38.30% vs. 25.97%, p < 0.001. With aRTD escalation, hazard ratios (HRs) of OS/DFS declined until aRTD exceeded 50Gy, then increased, whereas that of LRFS declined until aRTD exceeded 50 Gy, then remained steady. HR of treatment-related mortality was stable until aRTD exceeded 50 Gy, then increased. LRA revealed strong correlations between LRFS and OS/DFS (r = 0.984 and r = 0.952, respectively). An absolute 1% advancement in LRFS resulted in 0.32% and 0.34% improvements in OS and DFS. Conclusions: An aRTD of 50Gy was well-tolerated, with favorable survival resulting from PORT-related LRFS improvement in patients staged T3−4N0 or T1-4N1−3. Further stratification analyses based on tumor burden would help determine potential PORT-beneficiaries.

The long-term survival of the doublet regimen of concurrent chemoradiation therapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study

ObjectiveThis study introduces innovative strategies, the doublet regimen of concurrent chemoradiotherapy, to ensure longer survival for locoregionally advanced nasopharyngeal carcinoma.MethodsWe retrospectively reviewed 104 locoregionally advanced nasopharyngeal carcinoma patients who underwent taxane combined platinum-based concurrent chemoradiotherapy in our center between January 2013 and December 2018. All statistical analyses were performed using the Kaplan–Meier method (SPSS 23.0). Different groups were compared with the Wilcoxon rank-sum test.ResultsUltimately, 104 patients were selected for this study, including 18 and 86 who received either concurrent chemoradiation therapy alone or concurrent chemoradiation therapy plus adjuvant chemotherapy, respectively. The median follow-up time for progression free survival was 53.0 months (IQR 48.5–57.5). The 3-years progression-free survival (PFS), overall survival (OS), local–regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates of the doublet regimen of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma were 85.9%, 96.0%, 96.0% and 90.8%, respectively. Additionally, we analyzed the subgroups and found that the 3-years PFS, OS, LRRFS and DMFS rates for stage III versus stage IVa were 97.8% versus 75.5% (P = 0.000), 100% versus 92.5% (P = 0.004), 100% versus 92.4% (P = 0.015) and 97.8% versus 82.8% (P = 0.002), respectively. During concurrent chemotherapy, acute chemotherapy adverse events of grade 3 or 4 was only 18.3%. Leukopenia was the most common acute chemotherapy adverse event (in 10 patients [9.6%]), followed by neutropenia (in 8 patients [7.6%]).ConclusionThe doublet regimen of taxane plus platinum concurrent chemoradiotherapy resulted in improved long-term survival of locoregionally advanced nasopharyngeal carcinoma patients, especially for local control rate and warrants further prospective evaluation.

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump

This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit. Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared. Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017). The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

Intensity-modulated proton and carbon-ion radiation therapy in the management of major salivary gland carcinomas

Primary major salivary gland carcinomas (SGCs) present with diverse histological types that are known to be largely radioresistant with a high tendency to develop distant metastasis (DM). Photon-based radiotherapy (RT) is limited in terms of its therapeutic effect and toxicities. In view of the physical and biological advantages of intensity-modulated proton and/or carbon-ion radiation therapy, we aimed to evaluate the short-term therapeutic effect and toxicities in patients with major SGCs treated with this form of radiation therapy. Between August 2015 and November 2019, a total of 55 consecutive and non-selected major SGC patients who received particle RT at the Shanghai Proton and Heavy Ion Center (SPHIC) were retrospectively analyzed. The 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates, as well as prognostic factors were analyzed. Additionally, acute and late toxicities were also analyzed. With a median follow-up time of 24 (range, 6-57) months, the 2-year OS, PFS, LRRFS, and DMFS rates were 91.6%, 78.6%, 94.2%, and 83.9%, respectively. At the time of this analysis, four patients had developed local or regional recurrence, and seven additional patients had developed DM. Three patients had died due to disease progression, and another patient with recurrence experienced a late Grade 5 event (hemorrhage) at 9 months after re-irradiation with carbon ion and subsequently died. Otherwise, none of the patients had grade 3 or higher treatment-induced acute or late adverse effects except one who developed grade 3 acute mucositis. Overall, intensity-modulated proton and/or carbon-ion radiation therapy provided satisfactory therapeutic effectiveness in our major SGCs patients with a low incidence of acute and late toxicities.

Comparison of the efficacy and toxicity of postoperative proton versus carbon ion radiotherapy for head and neck cancers

To compare the efficacy and toxicity of adjuvant proton beam vs. carbon-ion beam radiotherapy for head and neck cancers after radical resection and to explore the value of particle beam radiotherapy (PBRT) in postoperative radiotherapy for head and neck cancers. Data from 38 head and neck cancer patients who received adjuvant PBRT after complete surgical resection at the Shanghai Proton and Heavy Ion Center (SPHIC) between October 2015 and March 2019 were retrospectively analyzed. In total, 18 patients received adjuvant proton beam therapy (54-60 GyE/27-30 fractions) and 20 received adjuvant carbon-ion radiotherapy (CIRT) (54-60 GyE/18-20 fractions). Survival rates were calculated using Kaplan-Meier analysis. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Effects (version 4.03). With a median follow-up time of 21 (range, 3-45) months, the 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 93.3%, 87.4%, 94.1%, and 90.7%, respectively, for the entire cohort. The rates after proton beam therapy vs. CIRT were 94.1% vs. 91.7% (P=0.96), 88.1% vs. 86.2% (P=0.96), 94.4% vs. 93.3% (P=0.97), and 88.1% vs. 92.9% (P=0.57), respectively. Furthermore, 16 of the 18 (88.9%) patients developed acute grade I/II dermatitis (13 grade I; 3 grade II) after proton beam therapy, and only 7 of the 20 (35%) patients developed acute grade I dermatitis after CIRT (P=0.001). The incidence of acute grade I/II mucositis and xerostomia in proton and carbon ion cases were 45% vs. 55% (P=0.75) and 56% vs. 50% (P=0.87) respectively. Adjuvant proton beam therapy and CIRT after radical surgical resection for head and neck cancers provided satisfactory therapeutic effectiveness, but no significant difference was observed between the two radiotherapy technologies. However, adjuvant CIRT was associated with a more favorable acute toxicity profile as compared to proton beam therapy with significantly lower frequency and severity of acute dermatitis observed.

Simultaneous Integrated Boost vs. Routine IMRT in Limited-Stage Small-Cell Lung Cancer: An Open-Label, Non-Inferiority, Randomized, Phase 3 Trial—Interim Analysis

<h3>Purpose/Objective(s)</h3> Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy. <h3>Materials/Methods</h3> This randomized, non-inferiority, open-label, phase 3 study was done in a single institution in China. Patients aged 18–70 years who was diagnosed with treatment-naïve and confirmed limited-stage SCLC were eligible. All participants received 4-6 courses of intravenous cisplatin 75 mg/m² or carboplatin (area under the curve 5–6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m² on days 1–3 every 3 weeks. Participants were randomly assigned (1:1) stratifying for the timing of thoracic radiation therapy to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F, PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F) to the primary lung tumor and CT positive lymph node metastases. Responders were offered prophylactic cranial irradiation of 25Gy/2.5Gy/10F.The primary endpoint was 2-year progression-free survival, the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity. <h3>Results</h3> Between February 2017, and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among which 106 patients in the conventional fractionated radiotherapy group,110 patients in the SIB group. The 2-year progression-free survival rates were 45.2% vs 38.3% and the median progression-free survival was 18 months (95%CI:9.06-26.39) in the conventional fractionated radiotherapy group versus 17 months(95%CI:11.47-22.53) in the SIB group (P=0.2, HR 1.22,95%CI:0.87-1.72). The 2-year overall survival rates were 73.5% VS 60.9% (P=0.14, HR 1.35,95%CI:0.90-2.04). The 2-year local-regional recurrence-free survival rates were 68.7% VS 69.9% (P = 1.0, HR = 0.98, 95% CI = 0.62-1.56). The most common grade 3–4 adverse events were myelosuppression (21.7% vs 15.4%, P = 0.83), radiation pneumonitis (4.7% vs 2.7%, P = 0.44), radiation esophagitis (3.8% vs 1.8%, P = 0.51). <h3>Conclusion</h3> Simultaneous integrated boost radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with limited-stage small cell lung cancer. Further enrollment and follow-up are warranted to confirm these findings in this ongoing trial. This trial is registered at ClinicalTrials.gov, NCT04500145.