Distant Metastasis-free Survival Research Articles

Selection of induction chemotherapy cycles for stage N3 nasopharyngeal carcinoma based on pre-treatment plasma EBV DNA.

This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA < 7800 copies/ml, both groups showed comparable survival outcomes. In terms of acute adverse reactions, the IC = 4 group experienced higher incidences, particularly with grade 2-4 alanine transaminase elevation and thrombocytopenia. For stage N3 NPC, pre-EBV DNA could be a powerful predictor for guiding the selection of IC cycles. The IC = 4 regimen is probably more beneficial to high-risk patients due to superior survival, while for low-risk patients, the IC = 3 regimen may be sufficient.

Serum non-high-density lipoprotein cholesterol predicts distant metastases following resection of stages I to III colorectal cancer.

The aim of this study was to examine the relationship between levels of non-high-density lipoprotein cholesterol (non-HDL-C) and postoperative distant metastasis for stages I to III colorectal cancer (CRC). Demographic, clinicopathological, and lipid data were collected from 588 patients, who were subsequently grouped according to their non-HDL-C levels. The primary endpoint was distant metastasis, survival without distant metastasis-free survival (DMFS). The association between non-HDL-C and pathological features, as well as postoperative distant metastasis, was assessed using a chi-square test, Mann-Whitney U test, and Cox proportional hazard regression model. The correlation between DMFS and non-HDL-C levels was analyzed employing the Kaplan-Meier method and log-rank test. The incidence of postoperative distant metastasis was significantly higher in the high non-HDL-C group (34.8%) compared to the low non-HDL-C group (18.2%) (P < .001). Non-HDL-C levels were significantly higher in the metastasis group than in the nonmetastasis group (P = .001). Multivariate Cox proportional hazards identified non-HDL-C ≥ 4.1mmol/L(HR: 2.604; 95% CI: 1.584-4.282; P = .001) as independent risk factors for postoperative distant metastasis. The high non-HDL-C group exhibited a higher rate of distant metastasis and a shorter duration of DMFS (HR: 2.133; 95% CI: 1.404-3.240; P < .001). Our study suggests that high levels of non-HDL-C (≥4.1 mmol/L) may potentially serve as predictors for postoperative distant metastasis in stages I to III CRC.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

What Is the Prognostic Value of the Pathologic Response after Neoadjuvant Radiotherapy in Soft Tissue Sarcoma? An Institutional Study Using the EORTC-STBSG Response Score.

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS.

Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

P16 status or response to induction chemotherapy, which predicts survival outcomes in Chinese oropharyngeal cancer treated with definitive radiotherapy?

PurposeTo identify whether p16 status or response to induction chemotherapy (IC) predicts the radiotherapy (RT) response and survival outcomes in Chinese oropharyngeal squamous cell carcinoma (OPSCC). MethodsA total of 211 patients, including 128 p16-positive and 83 p16-negative were analyzed. All patients underwent IC followed by definitive RT or concurrent chemoradiotherapy (CCRT). Propensity score matching (PSM) was used to eliminate the baseline variations. ResultsAge, sex, smoking history, alcohol history, and primary site were unbalanced between different p16 status subgroups. Before PSM, the objective response rates to IC between p16-positive and p16-negative groups were 80.5 % and 85.5 % (p = 0.344). After RT, the complete response (CR) rates were 73.4 % and 66.3 %, respectively (p = 0.264). IC-sensitive (IC-s) subgroups had a higher percentage of RT-CR rate than the IC-resistant (IC-r) subgroups in both p16-positive and p16-negative patients. IC-s showed significant improvement in cancer-specific survival (CSS) (92.9 % vs. 53.6 %, p < 0.0001), progression-free survival (PFS) (p < 0.0001), locoregional relapse-free survival (LRFS) (p < 0.0001) and distant metastasis-free survival (DMFS) (p = 0.025). After PSM, the CR rates among different p16 groups remained comparable following RT (71.2 % vs. 65.8 %, p = 0.476). Before or after PSM, CSS, PFS, LRFS, and DMFS were similar between different p16 status either in IC-s or IC-r subgroups (p > 0.05). IC-r was independently associated with shorter PFS (HR = 2.661, p = 0.002) and LRFS (HR = 2.876, p = 0.002; HR = 2.78, p = 0.018). ConclusionsResponse to IC is an important predictor of prognosis in Chinese OPSCC treated with definitive RT. Poor response to IC is associated with unsatisfactory outcomes either in p16-positive or p16-negative OPSCC.

Concurrent Chemoradiotherapy versus Radiotherapy Alone in the Treatment of Stage II and T3N0M0 Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

AimsThe efficacy of concurrent chemoradiotherapy (CCRT) for Stage II and T3N0 nasopharyngeal carcinoma (NPC), particularly during the shift from two-dimensional conventional radiotherapy (2DCRT) to intensity-modulated radiotherapy (IMRT) is debated.Therefore this study aims to systematically evaluate and meta-analyze survival benefits of CCRT versus radiotherapy alone for Stage II and T3N0 NPC, stratified by radiotherapy techniques. Materials and methodsAs of April 1, 2024, we conducted an exhaustive literature search across databases such as PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying and screening studies that compare the efficacy of CCRT versus radiotherapy alone in the treatment of Stage II and T3N0 NPC. ResultsA total of 10 studies encompassing 5015 patients were included in this comprehensive analysis. The findings indicate that, apart from progression-free survival (PFS), CCRT did not improve survival outcomes, including overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRRFS), and failure-free survival (FFS), with all P values exceeding 0.05. Concurrently, the incidence of grade ≥3 adverse events associated with CCRT was significantly elevated (odds ratio [OR] = 3.77, 95% confidence interval [CI] = 2.75–5.15, P < 0.0001). Subgroup analysis revealed that, compared with RT, the combination of 2DCRT with concurrent chemotherapy significantly improved OS (hazard ratio [HR] = 0.57, 95% CI = 0.46–0.71, P < 0.00001), PFS (HR = 0.65, 95% CI=0.53–0.78, P < 0.00001), DMFS (HR = 0.54, 95% CI = 0.37–0.79, P = 0.002), and LRRFS (HR = 0.63, 95% CI = 0.49–0.82, P = 0.0005). In contrast, the combination of IMRT with concurrent chemotherapy failed to demonstrate improvements in OS, PFS, DMFS, or LRRFS, with all P values exceeding 0.05. ConclusionIn contrast with RT, CCRT did not enhance survival in stage II and T3N0 NPC patients, yet caused more adverse reactions. 2DCRT combined with concurrent chemotherapy significantly improved OS, PFS, DMFS, and LRRFS, while IMRT with concurrent chemotherapy showed no clinical benefits.

Hypoxia-associated gene signatures are not prognostic in high-risk localised prostate cancers undergoing androgen deprivation therapy with radiotherapy

PurposeMen with high-risk prostate cancer (PCa) are treated with androgen deprivation therapy (ADT) and radiotherapy, but the disease reoccurs in 30% of patients. Biochemical recurrence of PCa after treatment is influenced by tumour hypoxia. Tumours with high levels of hypoxia are aggressive, resistant to treatment, and have increased metastatic capacity. Gene expression signatures derived from diagnostic biopsies can predict tumour hypoxia and radiosensitivity, but none are in routine clinical use, due to concerns about the applicability of these biomarkers to new patient cohorts. There has been no or limited testing in cohorts of high-risk PCa. Methods and materialsWe generated transcriptomic data for cohorts of high-risk PCa patients. Patients were treated with ADT followed by external beam radiotherapy with or without a brachytherapy boost. Biomarkers curated from the literature were calculated from pre-treatment biopsy gene expression data. The primary endpoint for survival analyses was biochemical recurrence-free survival (bRFS) and the secondary endpoints were distant metastasis-free survival (DMFS) and overall survival. ResultsThe performance of the selected biomarkers was poor, with none achieving prognostic significance for bRFS or DMFS in any cohort. The brachytherapy boost cohort received shorter durations of ADT than the conventionally fractionated or hypofractionated cohorts (Wilcoxon rank sum test, p=2.1 × 10-18 and 2.3 × 10-10 respectively) and had increased risk of distant metastasis (log-rank test, p=8 × 10-4). There were no consistent relationships between biomarker score and outcome for any of the endpoints. ConclusionsHypoxia and radiosensitivity biomarkers were not prognostic in high-risk PCa patients treated with ADT plus radiotherapy. We speculate that the lack of prognostic capability could be caused by the variable hypoxia-modifying effects of the ADT that these high-risk patients received before and during definitive treatment with radiotherapy. A deeper understanding of biomarker construction, performance and inter-cohort transferability in relation to patient characteristics, sample handling and treatment modalities is required before hypoxia biomarkers can be recommended for routine clinical use in the pre-treatment setting.

Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients

PurposeThe aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients. MethodsA total of 195 eligible early BC cases were tested for genomic risk between 2006 – 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics. ResultsMammaPrint identified 118 (60.5%) patients with genomically Low Risk tumors and 77 (39.5%) patients with genomically High Risk tumors. Age, menopausal status, tumor size, receptor status, and nodal status were comparable between MammaPrint Risk categories. The median follow-up was 8.4 years for DMFS and 9.3 years for OS; 8-year follow-up was reported for both endpoints. The 8-year DMFS was 90.4% (95% CI 84.9 – 95.9) in patients with MammaPrint Low Risk tumors compared to 60.8% (95% CI 49.8 – 71.8) for patients with High Risk tumors. Patients with MammaPrint Low Risk tumors exhibited significantly superior 8-year OS (97.3%; 95% CI 94.4 – 100) compared with MammaPrint High Risk tumors (89.5%; 95% CI 82.6 – 96.4; p = 0.028). Multivariate analyses identified MammaPrint as significantly associated with 8-year DMFS and MammaPrint together with Progesterone Receptor positivity with 8-year OS. ConclusionThe prognostic performance of MammaPrint was demonstrated in early-stage clinically intermediate to high-risk BC patients. Moreover, patients with MammaPrint Low Risk tumors had good outcome regardless of treatment regimen, thus supporting personalized treatment choices.

Correlation of dynamic blood dose with clinical outcomes in radiotherapy for head-and-neck cancer

Background and purposeRadiation-induced lymphopenia (RIL) during cancer radiotherapy is receiving growing attention due to its association with adverse clinical outcomes. Correlations between RIL and poorer locoregional control (LRC), distant-metastasis-free survival (DMFS), and overall survival (OS) have been demonstrated across multiple treatment sites. Estimates of radiation delivered to circulating blood or lymphocytes have been shown to be correlated with severe RIL. This study aims to evaluate whether blood dose estimates are equally correlated with patient outcomes directly. Materials and methodsFor 298 head-and-neck cancer patients, blood dose was estimated via the total body dose (Dbody), a static blood dose model considering the mean dose to relevant organs and tissues (Dstatic), and a dynamic model which further included temporal aspects such as blood flow and treatment delivery time (Ddynamic). The latter utilized hematological dose (HEDOS), an open-source computational tool for blood dose simulations. Survival analysis was performed to evaluate potential correlations between blood dose and LRC, DMFS, and OS. ResultsMultivariable Cox regression analysis found a statistically significant (p < 0.05) correlation between various dynamic blood dose metrics and clinical outcomes. Dbody and Dstatic did not correlate with any of the outcomes considered. ConclusionA statistically significant correlation between the dynamic blood dose model and adverse clinical outcomes was observed. During multivariable regression analysis, neither static blood dose model exhibited a statistically significant correlation with any of the outcomes studied.

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma

PurposeTo investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. Methods950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. ResultsTumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. ConclusionsThe earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

P4.07F.01 Real World Characteristics and Distant Metastasis Free Survival of Patients with Early NSCLC Treated with Chemoimmunotherapy

P4.07F.01 Real World Characteristics and Distant Metastasis Free Survival of Patients with Early NSCLC Treated with Chemoimmunotherapy

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study.

A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice. Patients operated for early-stage ER+ breast cancer with disputable chemotherapy indication, had been prospectively included between 2013 and 2015. Oncologists were asked whether they intended to administer adjuvant chemotherapy before deployment of the 70-GS test. Information on adjuvant systemic treatment and oncological outcome was obtained through active follow-up by data managers of the Netherlands Cancer Registry. The primary endpoint of this study was distant metastasis-free survival (DMFS) according to the genomic risk. Exploratory analyses were done to evaluate DMFS in relation to the oncologists' pre-test advice. After a median follow-up of 7 years, distant metastases were diagnosed in 23 of the 606 patients (3.8%) and 36 (5.9%) patients had died. The DMFS rate for the 357 70-GS genomic low-risk patients was 94.2% (95% CI 91.2-96.2) and 89.1% for the 249 genomic high-risk patients (95% CI 84.3-92.4). Of the low-risk patients 3% had received chemotherapy compared to 80% of the high-risk patients. For the subgroups based on the pre-test oncologists' advice (no chemotherapy/chemotherapy/unsure) there were no clinically relevant differences in DMFS (89.8, 93.2 and 92.0%, respectively), while comparable proportions of patients had received chemotherapy. In patients with early-stage ER+ breast cancer with a disputable chemotherapy indication it is sensible to deploy the 70-GS to better select patients for adjuvant chemotherapy.

Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

Unilateral radiotherapy for tonsillar cancer with multiple ipsilateral neck lymph nodes.

For tonsillar cancer with multiple ipsilateral neck lymph nodes, the safety and efficacy of unilateral radiotherapy (RT) have long been a topic of debate. We performed retrospective analyses of patients having ipsilateral neck lymph nodes treated with unilateral RT in two tertiary referral hospitals. This study accrued 29 patients who were diagnosed as well-lateralized tonsillar cancer with multiple ipsilateral neck lymph nodes and underwent unilateral RT from March 2000 to March 2020. Patients underwent treatment with one of the following options or a combination of them: induction chemotherapy, surgery, RT, and concurrent chemoradiotherapy. We analyzed the recurrence pattern and survival with special attention to contralateral neck failure. Also, treatment-related toxicities were compared with a 1:1 matched cohort of those who received bilateral RT, using propensity score matching analysis. At a median follow-up of 68 months, no contralateral neck failure was observed. Five-year actuarial locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 85.6%, 91.8%, and 92.7%, respectively. Both the acute and chronic grade 2 xerostomia occurred in 10.3% of the patients. When the toxicity for unilateral RT was compared to that of bilateral RT using a propensity score-matched cohort, a significantly lower rate of acute xerostomia was observed in unilateral RT group (55.1% vs. 82.7%, p=0.002), primarily at grade 2 level (10.3% vs. 51.7%, respectively). The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph nodes.

Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy.

This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC). We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45-65 Gy in 15-30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan-Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model. During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00-3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57-14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI. In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p <0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

Lipid profiling of RON and DEK-dependent signaling in breast cancer guides discovery of gene networks predictive of poor outcomes.

Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK oncoproteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but their influence on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, a nuclear magnetic resonance (NMR)-based approach was utilized. The observed differences identified a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis-free survival (DMFS), post-progression survival (PPS), and recurrence-free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, whereas DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts poor outcomes for patients with breast cancer patients. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence.

Comparing long-term efficacy and safety of GP versus TPF sequential chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis

PurposeTo evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsFrom 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups.ResultsA total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema.ConclusionNo significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

Patterns of treatment failure in patients with sinonasal squamous cell carcinoma after chemoradiotherapy.

To investigate the failure patterns based on precision radiation treatment and to determine the predictive factors of treatment failure for sinonasal squamous cell carcinoma (SNSCC) patients. This was a retrospective study that included 214 cases of treatment failure from 441 consecutive patients. Two experienced radiation oncologists evaluated the tumour volume of cases with local recurrence. The 5-year overall survival (OS), progression-free survival (PFS) rates, and distant-metastasis-free survival (DMFS) were estimated. Investigations were performed on the factors that predicted local failure or distant metastasis. About 140 (31.7%) patients developed local recurrence, 24 (5.4%) experienced regional failure, and 65 (14.7%) underwent distant metastasis. In-field, marginal, and out-of-field failures occurred in 55.7% (78/140), 33.6% (47/140), and 10.7% (15/140) of patients with local recurrence, respectively. In logistic regression analysis, factors statistically significant for total local failure included treatment mode (P < .01), chemotherapy (P < .01), and surgical margins (P < .01). Primary tumours with poor differentiation (P = .018) and R2 resection margin (P = .009) were more prone to develop distant failure. The 5-year OS, PFS, and DMFS rates were 57.8%, 52.0%, and 56.7% for the whole cohort. In univariate and multivariate analysis, the skull base involvement was an independent predictor for poorer OS and PFS; orbital invasion was an independent predictor for poorer OS. Local recurrence and distant metastasis were the most common failure modes. Treatment mode, chemotherapy, and surgical margins were related to local recurrence. Poor differentiation and R2 resection margin were predictors for distant failure. Local recurrence is the most common failure pattern in patients with SNSCC who accepted chemoradiotherapy, and marginal and out-of-field failures occurred in 44.3% of patients with local recurrence.