Independent Prognostic Factor For DMFS Research Articles

Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma

BackgroundTo compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment.MethodsWe retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors.ResultsThe median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group.ConclusionsFor NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Reflecting on the utility of standardized uptake values on 18F-FDG PET in nasopharyngeal carcinoma.

BackgroundTo rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET).MethodsWe retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan–Meier and Cox regression analyses were used to assess survival.ResultsThe optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039–3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021–2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214–5.325, P = 0.013).ConclusionHigh SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-022-09626-w.

Failure Patterns of Recurrence and Metastasis After Intensity-Modulated Radiotherapy in Patients With Nasopharyngeal Carcinoma: Results of a Multicentric Clinical Study.

PurposeThis study aimed to explore factors associated with recurrence and metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and provide evidence for NPC treatment.MethodsWe retrospectively analysed the treatment dose and survival outcomes of 645 patients with nasopharyngeal carcinoma without distant metastases treated with IMRT for the first time at three treatment centres in the Guangxi Zhuang Autonomous Region, China, between January 2009 and December 2012.ResultsThere were 9.3% of patients (60/645) had recurrence and 17.5% (113/645) had distant metastasis 5 years after treatment. The 1-year, 3-year and 5-year local recurrence rates were 0.9%, 6.5% and 9.0% respectively. And the 1-year, 3-year and 5-year distant metastasis rates were 3.4%, 10% and 17.2%, respectively. In the 60 patients with recurrence, the in-field, marginal-field, and out-field recurrence rates were 93.3% (56/60), 5.0% (3/60) and 1.7% (1/60), respectively. Recurrence failures occurring within the first three years after treatment accounted for 81.7% (49/60). In the 113 patients with metastasis, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, the residual cervical lymph node size and the time of residual cervical lymph node complete response (CR) were independent prognostic factors for DMFS (P <0.05).ConclusionMost recurrences occured in the first three years after IMRT. In-field recurrence was the most common pattern for loco-regional failure of NPC treatment. The risk of distant metastasis was positively correlated with higher N stage, lower neck nodal metastasis, larger size of cervical lymph nodes, and longer time to response for residual NPC in cervical adenopathy.

A randomized phase II trial of diffusion-weighted MR imaging-guided radiotherapy plus chemotherapy versus standard chemoradiotherapy in locoregional advanced nasopharyngeal carcinoma.

6018 Background: We hypothesized that diffusion-weighted MR imaging (DWI) guided dose-painting radiotherapy (DP-RT) was associated with improved tumor control and survival compared with standard CT-based radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized phase II trial was to compare the efficacy and toxicity of DWI guided DP-RT plus chemotherapy versus standard CT-based radiotherapy plus chemotherapy in locoregionally advanced NPC. Methods: Two hundred and fifty-six patients with stage III-IVa (8th AJCC) NPC were randomly assigned to receive DWI-guided dose-painting radiotherapy plus chemotherapy (DP-RT group, n = 128) or standard CT-based radiotherapy plus chemotherapy (CT-based RT group, n = 128). Patients in both groups received 3 cycles of induction chemotherapy followed by cisplatin-based concurrent chemoradiotherapy. In DP-RT group, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC &lt; mean). The dose to GTVnx-DWI was escalated to DT 75.2 Gy/32 Fx in patients with T1-2 disease, and DT 77.55 Gy/33 Fx in those with T3-4 disease, in 2.35 Gy per fraction. In CT-based RT group (n = 128), PGTVnx was irradiated at DT 70.4-72.6 Gy/32-33 Fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn, number ChiCTR1800015779. Results: Compared with standard CT-based radiotherapy, DWI-guided DP-RT significantly improved 2-year local recurrence-free survival (LRFS, 100% vs. 95.4%; P = 0.024), distant metastasis-free survival (DMFS, 97.9% vs. 90.6%; P = 0.006), disease free survival (DFS, 93.2% vs. 86.8%; P = 0.021), and overall survival (OS, 100% vs. 95.2%; P = 0.038). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (DWI-guided DP-RT vs CT-based RT without DP) was a significant independent prognostic factor for DMFS and DFS (P = 0.021 and P = 0.020, respectively). Conclusions: Diffusion-weighted MR imaging guided dose-painting radiotherapy plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity, as compared with standard CT-based radiotherapy plus chemotherapy, among patients with locoregionally advanced nasopharyngeal carcinoma. Clinical trial information: ChiCTR1800015779.

Analysis Of Clinical Outcome, Toxicity And Prognosis On Locally Advanced Cervical Squamous Cell Carcinoma With Normal SCCAg Levels Receiving Intensity-Modulated Radiotherapy, Brachytherapy Combined With Concurrent Chemotherapy

Though SCCAg could be a useful marker in squamous cell carcinoma, rising of SCCAg is not demonstrated in some patients with squamous cell cancer. This study aimed to assess the clinical outcome, toxicity and prognosis on locally advanced cervical squamous carcinoma with normal SCCAg levels receiving concurrent chemoradiotherapy. A total of 294 patients of locally advanced cervical squamous cell carcinoma with normal SCCAg levels before treatment, FIGO 2018 staging from IB to IIIC2 with a median age of 54 years old, who received concurrent chemoradiotherapy from 2007 to 2016 were evaluated in this study. All patients received intensity-modulated external radiotherapy, high-dose-rate brachytherapy and cisplatin-based concurrent chemotherapy. 57 patients (19.39%) were diagnosed with pelvic lymph node metastasis before treatment, 32 (10.88%) of which were unilateral pelvic lymph node metastasis, and 25 (8.5%) were bilateral pelvic lymph node metastasis. The median survival time was 69.1 months, with 5-year OS, DFS, LCR and DMFS 83.6%, 80.6%, 90.3% and 88.1% respectively. 28 patients (9.52%) had local recurrence and 35 (11.9%) had distant metastasis. 11.56% and 1.02% patients had Grade III acute and late adverse effects in urinary system with 8.16% and 1.02% in gastrointestinal tract. The occurrence of the above for Grade IV were only 0%, 0%, 0% and 0.34%. Grade III acute hematological adverse events in leukocytes and neutrophils, lymphocytes, hemoglobin and platelets were 46.26%, 54.42%, 26.87%, 4.76% and 4.08%. Those of grade IV were 3.06%, 30.95%, 3.40%, 0.68% and 0.00%. Grade III late hematological toxicity, leukocytes, neutrophils, hemoglobin and platelets were 2.72%, 0.68%, 3.06% and 0.34%. Those of grade IV all show as 0.34%. As for prognostic factors, EQD2≥8500cGy (P = 0.001 and 0.008) and the courses of concurrent chemotherapy ≥4 cycles (P = 0.024 and 0.018) substantially improve OS and DFS. The performance of brachytherapy (P = 0.000) effectively improved LCR. While the courses of concurrent chemotherapy ≥ 4 cycles (P = 0.024) acted as an independent prognostic factor for DMFS, pelvic lymph node metastasis was an independent prognostic factor for OS, DFS, LC and DMFS, with metastasis of bilateral pelvic lymph nodes leading to worse prognosis than that of unilateral one. Intensity-modulated radiation therapy combined with brachytherapy and at least 4 courses of concurrent chemotherapy could significantly improve the prognosis including local recurrence and distant metastasis of locally advanced cervical squamous cell carcinoma with normal SCCAg level, and substantially reduce incidence of acute and late adverse effects above grade III. Most importantly, metastasis of pelvic lymph nodes acted as a significant prognosis factor. Among metastases of pelvic lymph nodes, bilateral metastases had a worse prognosis than unilateral ones.

Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

BackgroundLymph node metastasis in the cervical region posterior to level V (PLV) can occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.MethodsWe retrospectively studied 605 cases of NPC diagnosed by pathological detection from December 2011 to November 2017. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.ResultsLymph node metastasis occurred in 557 (92.06%) of 605 patients. There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean vertical distance of the central point of each lymph node from the anterior surface of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P = 0.018), level Va, level Vb, and level Vc lymph node metastasis (all P < 0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6, 27.7, 89.1, and 47.3%, respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P < 0.05).ConclusionNPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. We recommend that the margin of the PLV region may be a new cervical lymph node segment for NPC.

The failure patterns and related factors of nasopharyngeal carcinoma treated by intensity modulated radiation therapy in Xiangxi area

Objective To analyze the failure patterns and related factors of intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) in Xiangxi. Methods 107 patients with nasopharyngeal carcinoma without distant metastasis were selected from December 2012 to June 2015 in the first affiliated hospital of Jishou University. Locoreginal recurrence-fee survival rate (LRFS), distant metastasis-free survival rate (DMFS) and progression-free survival (FPS) rate were collected. The survival rate was analyzed by Kaplan-Meier method, univariate analysis was analyzed by Logrank method, and multivariate analysis was analyzed by Cox regression. Results Tumor progression occurred in 40 cases of 107 patients with nasopharyngeal carcinoma. Among them, 14 cases(13.1%) had local recurrence and 33 cases (30.8%) had distant metastasis. Univariate analysis showed that there was significant difference in LRFS between different ages and T staging (P<0.05). There was significant difference in DMFS and PFS between different gender, ages, diabete history, smoking history, T staging, N stage, clinical stage and treatment mode (P<0.05). Multivariate analysis showed that age and T staging were independent prognostic factors for LRFS. Age, T staging and N staging were independent prognostic factors for DMFS. Age, diabetes, T staging, and N staging were independent prognostic factors for PFS (P<0.05). Conclusions Distant metastasis is still the main model of treatment failure of NPC. Age, T staging and N staging before treatment are the significant prognostic factors. Key words: Nasopharyngeal neoplasms; Radiotherapy, intensity-modulated; Prognosis; Factor analysis, statistical

Lymph node metastasis and prognostic value of NPC based on the UICC lymph node staging for cervical lymph node levels.

e18136 Background: Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The neck lymph node (LN) metastasis is very common in NPC; it plays an important role in tumor staging which is guide the choice of treatment. Methods: 324 patients were pathologically diagnosed as non-metastatic NPC from Jan. 2005 to Dec.2010 were recruited retrospectively to analysis. All of them treated with standard IMRT. The clinical data including CT/MRI images, followed up were collected, while the OS, DFS, DMFS and RRFS were calculated. Survival analysis was performed by Kaplan-Meier method, and COX regression model was used for multivariate analysis. Results: The median follow-up time was 66 months (6-134 months). The 5-year LRFS,NRFS,DMFS,DFS and OS was 93.5%, 97.4%, 73.4%, 69.1% and 79.2%,respectively. The most common metastatic LN levels were II level 83.9%, retropharyngeal LN level 69.1%, followed by III level 16.9%, Va level 8% ,IV level 5.2% and Vb level 4%. All the retropharyngeal LNs were involved in the lateral group while no medial ones was found. In cervical LN, necrosis was involved in 40.0% patients with positive nodes and extracapsular invasion was noted in 58.6%. Bilateral positive LN was involved in 66.5%, and there was 11.4% in the lower cervical region. Univariate analysis showed that LN diameter greater than 3 cm, extracapsular invasion, LN necrosis and LN laterality are independent prognostic factors for DMFS and DFS (P &lt; 0.05). T staging and N staging were independent prognostic factors for the DMFS (P = 0.024, 0.012, respectively). Lower cervical involvement had no significant effect on DMFS and DFS. Multivariate analysis showed that T staging, extracapsular invasion and laterality were independent prognostic factors (P &lt; 0.05) for DFS, and extracapsular invasion was an independent prognostic factor (P = 0.048) for DMFS. Conclusions: Our results suggested II level and retropharyngeal LN have the highest metastasis rate. All retropharyngeal LN were involved in the lateral group but not medial one. Laterality, maximum diameter and necrosis are independent prognostic factors for DFS and DMFS. The involvement of the lower cervical region had no significant effect on DFS and DMFS.

Low BRMS1 expression promotes nasopharyngeal carcinoma metastasis in vitro and in vivo and is associated with poor patient survival

BackgroundBreast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients.MethodsBRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154).ResultsBRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC.ConclusionsLow expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.

Disseminated Tumor Cells of Breast Cancer Patients: A Strong Prognostic Factor for Distant and Local Relapse

Clinical significance of disseminated tumor cells (DTC) in bone marrow of early breast cancer patients has been reported, but improvements in detection methods are needed. Bone marrow aspirates from 621 patients with stage I to III breast cancer were screened for cytokeratin-positive (CK+) cells. CK+ cells were categorized into DTC only if they had specific morphologic features of tumor cells. Bone marrow status and clinical and pathologic variables of the patients were correlated with clinical outcome after a median follow-up of 56 months. DTC and non-DTC CK+ cells were detected in 15% and 34% of patients, respectively, with no correlation with clinical and pathologic variables. On univariate analysis, DTC detection was associated with a poorer distant metastasis-free survival (DMFS; P = 0.0013) and overall survival (OS; P = 0.005). Moreover, DTC detection was also associated with local relapse-free survival (P = 0.0009). On multivariate analysis, DTC detection was an independent prognostic factor for DMFS, local relapse-free survival, and OS. There was no significant interaction between DTC detection and hormonal receptors status (P = 0.34). Non-DTC CK+ cells had no clinical significance. DTC detection is a powerful prognostic marker for DMFS and OS in early breast cancer patients and can be individualized from irrelevant non-DTC CK+ cells by morphologic criteria. Biologically, despite high rates of systemic adjuvant therapy and locoregional irradiation in this series, DTC detection remains a prognostic factor of distant and, more strikingly, of local relapse, in favor of resistance to treatment of locally or distant disseminated cancer cells in DTC-positive patients.