M. Li

Management of salivary gland carcinomas - a review

Salivary gland carcinomas are a heterogeneous group of tumors with many histological subtypes which occur in both major and minor salivary glands. However, they have a relatively low of incidence. Their rarity limits study size and the ability to perform phase III trials. Therefore, to date, the entire management is usually varied. Certain published studies have paid more attention to the systemic therapy in the management of metastatic or locally recurrent salivary gland cancer, while little effort has been made to study the entire management for this lesions. Although results of treatment for patients with salivary gland carcinoma have improved in recent years, the treatment of salivary gland cancers is still not standardized. And some patients who haven’t received optimal treatment strategies had a reduced survival. In this review, the topics covered include surgery and radiotherapy, selective neck dissection, chemotherapy, and targeted therapy, which aimed to summarize the optimal management approaches and to develop recommendations for managing this lesions. For these rare cancers, there is also a need for a determined, coordinated effort to conduct high-quality clinical trials.

The lymphocyte–monocyte ratio predicts tumor response and survival in patients with locally advanced esophageal cancer who received definitive chemoradiotherapy

Background The lymphocyte–monocyte ratio (LMR), a simple biomarker that can reflect the antitumor immune response of the host, has been associated with patient prognosis in several solid tumors. The aim of this study was to evaluate whether LMR can predict clinical tumor response and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received definitive chemoradiotherapy (CRT). Patients and methods A total of 162 advanced ESCC patients treated at our institution between January 2012 and December 2013 were retrospectively recruited for analysis. Patients were treated with a platinum-based bimodal cytotoxic drug chemotherapy and concurrent radiation therapy. The LMR was calculated from blood counts in samples collected prior to treatment initiation. The predictive value of LMR for clinical tumor response and prognosis was examined. Results The LMR before CRT was significantly higher in 48 patients who achieved clinical complete response (CR) compared to that in patients who did not achieve clinical CR (4.89±1.17 vs 3.87±1.29, P<0.001). Compared to their matched counterparts, patients in the high LMR group (LMR >4.02) showed a good clinical tumor response (P<0.05). A significant independent association between a high pretreatment LMR and better outcomes was identified in a multivariate analysis for progression-free survival (PFS; hazard ratio [HR]=2.17; P<0.001) and overall survival (OS; HR=2.02; P=0.002). Conclusion In ESCC patients, a high LMR before treatment, which indicates a robust host immune system, is associated with both a good clinical tumor response after definitive CRT and favorable prognosis.

Identification of risk factors and the pattern of lower cervical lymph node metastasis in esophageal cancer: implications for radiotherapy target delineation.

Radiotherapy remains the important therapeutic strategy for patients with esophageal cancer (EC). At present, there is no uniform opinion or standard care on the range of radiotherapy in the treatment of EC patients. This study aimed to investigate the risk factors associated with lower cervical lymph node metastasis (LNM) and to explore the distribution pattern of lower cervical metastatic lymph nodes. It could provide useful information regarding accurate target volume delineation for EC. We identified 239 patients who initial diagnosed with esophageal squamous cell carcinoma. The clinicopathological factors related to LNM were analyzed and the locations of the lower cervical metastatic lymph nodes were transferred onto computed tomography images. The lower cervical area was further divided into four subgroups areas. The results showed that the incidence of lower cervical LNM was 37.2 % (89 of 239) and 94.4 % (84 of 89 patients) patients had subgroup II and/or subgroup III region LNM. Of those patients, 151 nodes were considered to be clinical metastatic in the lower cervical region and 96% nodes were located in group II and group III. Based on the present study, prophylactic irradiating to lower cervical areas is recommended for patients with deeper tumor invasion, the mediastinal level 1, 2, and 4 station LNM and the more number of LNM. The atlas showed that, for the lower cervical area, the subgroup II and III region should be precisely covered in the target volume and the subgroup I and IV may be spared for minimizing the toxicity.

Radiotherapy for esophageal carcinoma: dose, response and survival

Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor) after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients.

18 F-fluorodeoxyglucose positron emission tomography predicts lymph node responses to definitive chemoradiotherapy in esophageal squamous cell carcinoma patients

Purpose To evaluate the capability of 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG-PET/CT) to predict the clinical response of metastatic lymph node (mLN) to definitive chemoradiotherapy (dCRT) and guide personalized radiation dose in esophageal squamous cell carcinoma (ESCC) patients. Patients and methods One hundred and forty-three mLNs from 59 patients with ESCC treated with dCRT and who had undergone a pretreatment 18F-FDG-PET/CT scan were included in the study. All defined mLNs were contoured by nuclear medicine radiologists. Response was evaluated by contrast-enhanced computed tomography and 18F-FDG-PET/CT. Results Sixty-nine mLNs showed complete response (CR), and 74 mLNs showed non-complete response. The 143 mLNs were divided into 4 groups (Groups 1–4) based on the quartiles of maximum standardized uptake value (SUVmax-G1, SUVmax-G2, SUVmax-G3, and SUVmax-G4) and metabolic tumor volume (MTV-G1, MTV-G2, MTV-G3, and MTV-G4). The CR rate of SUVmax-G2 was significantly higher than the other 3 groups. The escalated radiation dose improved the CR rate of lymph nodes in SUVmax-G3 (55 Gy) and SUVmax-G4 (61 Gy). The lowest CR rate was found in MTV-G4 (the group with the largest MTV). The escalated radiation dose (59.7 Gy) improved the CR rate of lymph node in MTV-Groups 3 and 4. Conclusion Pretreatment metabolic parameters can predict the response of mLNs to dCRT for patients with ESCC. The parameters could also be used to guide personalized dose to mLNs.

Clinical and radiological characteristics of central pulmonary adenocarcinoma: a comparison with central squamous cell carcinoma and small cell lung cancer and the impact on treatment response

Purpose The proportion of central pulmonary adenocarcinoma (ADC) in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs) and squamous cell carcinomas (SQCCs) and investigated the impact of these characteristics on patients’ treatment response. Patients and methods The medical records of 302 consecutive patients with central lung cancer from July 2014 to September 2016 were retrospectively reviewed. There were 99 patients with ADC, 95 with SQCC and 108 with SCLC. Computed tomography images were interpreted by two radiologists. Treatment response was determined by Response Evaluation Criteria In Solid Tumors 1.1. Results Univariate analyses found that younger age, female sex, no history of smoking, higher levels of carcinoembryonic antigen (CEA), contralateral hilum lymphadenopathy, contralateral lung metastasis, pleural nodules and pleural metastasis to the interlobular fissure were significantly correlated with central ADC. Multivariate logistic regression analyses revealed that compared with central SQCC, female sex, younger age, no history of smoking, higher levels of CEA and contralateral hilum lymphadenopathy were the significantly independent indicators of central pulmonary ADC. Furthermore, compared with central SCLC, younger age, higher levels of CEA and cytokeratin 19 fragment (Cyfra21-1), lower levels of neuron-specific enolase, pleural nodules and lack of vascular involvement were significantly associated with central ADC. In 85 central ADC patients who received first-line platinum-based chemotherapy, both univariate and multivariate logistic regression analyses revealed that pulmonary emphysema had a negative correlation with treatment response (odds ratio=8.04, p=0.02). Conclusion Our study revealed that central pulmonary ADCs exhibited more aggressive clinical and radiological characteristics. Pulmonary emphysema was an independent and negative indicator for treatment response of central ADC.

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma–a review

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

Background Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC). However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC. Patients and methods A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients. Results The rates of lymph node (LN) metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033). Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037). The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis. Conclusion For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy.

Mapping patterns of nodal metastases in esophageal carcinoma: rethinking the clinical target volume for supraclavicular nodal irradiation

BACKGROUND To map detail distribution of metastatic supraclavicular (SCV) lymph nodes (LN) in esophageal cancer (EC) patients and determine the precise radiation therapy clinical target volume (CTV). METHODS A total of 101 thoracic esophageal carcinoma patients after surgery experienced SCV LN metastasis were retrospectively examined. The SCV region is further divided into four subgroups. Using hand drawings registration, nodes were mapped to a template computed tomogram to provide a visual impression of nodal frequencies and anatomic distribution. RESULTS In all, 158 nodes were considered to be clinical metastatic in the SCV region in the 101 patients, 74 on the left and 84 on the right. Seven of 158 (4.4%) positive LN were located in group I, 78 of 158 (49.37%) were located in group II, 72 of 158 nodes (45.6%) were located in group III, 1 of 158 (0.63%) located in group IV. CONCLUSIONS According to our results, the SCV group II and group III are considered to be the high risk regions of esophageal squamous cell carcinoma (ESCC) LN metastasis, which were defined as elective nodal irradiation (ENI) areas.