Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma.
ABSTRACT: This case report presents a HIV-positive 60-year old male with Merkel cell carcinoma of his right forearm and pulmonary sarcoidosis, who, after excisions and irradiations of the primary tumour site and subsequent lymph node metastases developed distant metastases. He received radiotherapy to symptomatic mediastinal lymph node metastases followed by Doxorubicin and, after two cycles, by the PD-1 inhibitor Pembrolizumab due to mixed response. Re-staging showed a para-mediastinal, radiotherapy-induced pneumonitis, which was treated by prednisolone due to clinical symptoms. In September 2017, the patient developed a solitary lymph node metastasis next to the right atrium, for which he received stereotactic radiotherapy. The systemic treatment with Pembrolizumab was replaced by the PD-L1 inhibitor Avelumab and is being continued since. The patient has been in complete remission for one year now and the HIV-infection is well-controlled.
Project description:The Abscopal effect is a rare phenomenon observed in the treatment of metastatic cancer, where localized irradiation causes a response in non-irradiated tumor sites. Due to the recent success of immunotherapies, the Abscopal effect of radiation therapy has received renewed clinical interest. However, there is limited knowledge regarding the Abscopal effect and radiotherapy treatment of patients with esophageal carcinoma. The present study reports the case of a 65-year-old male patient, who presented with esophageal carcinoma and lymph node metastasis. A transthoracic esophagectomy with left cervical, mediastinal and abdominal lymphadenectomies was performed. A total of 4 cycles of chemotherapy and maintenance therapy with Pembrolizumab was performed until September 2016. Metastases in the left retroperitoneal lymph node in addition to extensive metastases to the pelvic lymph node were observed. The patient received Cyberknife radiotherapy with a dose of 42 Gy in 6 daily fractions targeted at the left retroperitoneal lymph node. Two months after radiation therapy, a positron emission tomography-computed tomography scan revealed complete regression of all lymph node metastases. There is increasing clinical evidence supporting the efficacy of the Abscopal effect, which may be initiated by high-dose radiation. Further research is required to make the Abscopal effect clinically relevant, however it may have potential as a treatment option.
Project description:To evaluate the pattern of lymph node metastasis (LNM) according to primary tumor location in T1 and T2 stage non-small cell lung cancer (NSCLC) patients.The data of 1916 NSCLC patients with LNM who underwent surgery with systematic nodal resection between November 2008 to December 2014 were included in the study. Analyses of tumor location, pathological T stage, and nodal metastasis were performed.In T1a stage patients, superior mediastinum, aortopulmonary, and inferior mediastinum lymph node metastases were observed in primary tumors present in the right upper lobe (RUL), left upper lobe (LUL) and right middle lobe (RML), respectively. In T1b-stage patients, superior mediastinum, aortopulmonary, and inferior mediastinum lymph node metastases were observed in the RML, LUL, and right lower lobe (RLL), respectively. In patients with T2a-stage, superior mediastinum, aortopulmonary and inferior mediastinum lymph node metastases were observed in the RUL, LUL, and RLL, respectively. However, in T2b-stage patients, RUL, LUL and RML locations were associated with superior mediastinum, aortopulmonary, and inferior mediastinum lymph node metastases, respectively. Multivariable logistic regression showed that T stage was significantly associated with mediastinal and intrapulmonary lymph node metastases. In addition, tumor location was significantly associated with N2 station LNM.LNM varied according to tumor location and T-stage, which are independent factors influencing N2 station LNM.
Project description:<h4>Background</h4> Squamous cell cancers in the hypopharynx (HP) and cervical esophagus (CE) are different diseases with different staging systems and treatment approaches. Pharyngoesophageal junction (PEJ) tumor involves both the hypopharynx and the cervical esophagus simultaneously, but few reports focused on PEJ tumors. This study aimed to clarify clinical characteristics and the treatment approaches of PEJ tumors. <h4>Patients and Methods</h4> A total of 222 patients with squamous cell carcinoma in the HP, PEJ, and CE were collected between January 2008 and June 2018 in Fudan University Shanghai Cancer Center. We compared different lymph node metastatic patterns of three diseases above and the survival of different tumor locations, different lymph node metastasis, and different radiotherapy approaches. <h4>Results</h4> For HP, PEJ, and CE cancer, the upper and middle cervical lymph node metastatic rates were 85.7%, 47.1%, and 5.8%, respectively; the lower cervical lymph node metastatic rates were 36.7%, 42.9%, and 35.0%, respectively; and the mediastinal lymph node metastatic rates were 2.0%, 72.9%, and 80.6%, respectively. The 3-year overall survival rates were 69.5% in the HP group, 52.0% in the PEJ group, and 69.6% in the CE group (p = 0.024). No survival differences were found between the involved-field-irradiation and elective-node-irradiation subgroups among PEJ tumors (p = 0.717 for OS and p = 0.454 for PFS, respectively). <h4>Conclusion</h4> HP cancers had a high prevalence in all cervical lymph node metastases, while CE cancers had a lower prevalence in the cervical and mediastinal lymph node metastases. PEJ cancer had the combined metastatic patterns of both HP and CE cancers. Involved field irradiation was feasible in chemoradiotherapy for PEJ cancers.
Project description:It is important to detect mediastinal lymph node metastases in patients with lung cancer to improve outcomes, and it is possible that activatable fluorescence imaging with indocyanine green (ICG) can help visualize metastatic lymph nodes. Therefore, we investigated the feasibility of applying this method to mediastinal lymph node metastases in an epidermal growth factor receptor (EGFR)-positive squamous cell carcinoma of the lung. Tumors were formed by injecting H226 (EGFR-positive) and H520 (EGFR-negative) cell lines directly in the lung parenchyma of five mice each. When computed tomography revealed tumors exceeding 8 mm at their longest or atelectasis that occupied more than half of lateral lung fields, a panitumumab (Pan)-ICG conjugate was injected in the tail vein (50 ?g/100 ?L). The mice were then sacrificed 48 hours after injection and their chests were opened for fluorescent imaging acquisition. Lymph node metastases with the five highest fluorescent signal intensities per mouse were chosen for statistical analysis of the average signal ratios against the liver. Regarding the quenching capacity, the Pan-ICG conjugate had almost no fluorescence in phosphate-buffered saline, but there was an approximate 61.8-fold increase in vitro after treatment with 1% sodium dodecyl sulfate. Both the fluorescent microscopy and the flow cytometry showed specific binding between the conjugate and H226, but almost no specific binding with H520. The EGFR-positive mediastinal lymph node metastases showed significantly higher average fluorescence signal ratios than the EGFR-negative ones (n = 25 per group) 48 hours after conjugate administration (70.1% ± 4.5% vs. 13.3% ± 1.8%; p < 0.05). Thus, activatable fluorescence imaging using the Pan-ICG conjugate detected EGFR-positive mediastinal lymph node metastases with high specificity.
Project description:Lymph node status is a major determinant of stage and survival in patients with lung cancer; however, little information is available about the expected yield of a mediastinal lymphadenectomy.The American College of Surgeons Oncology Group Z0030 prospective, randomized trial of mediastinal lymph node sampling vs complete mediastinal lymphadenectomy during pulmonary resection enrolled 1,111 patients from July 1999 to February 2004. Data from 524 patients who underwent complete mediastinal lymph node dissection were analyzed to determine the number of lymph nodes obtained.The median number of additional lymph nodes harvested from a mediastinal lymphadenectomy following systematic sampling was 18 with a range of one to 72 for right-sided tumors, and 18 with a range of four to 69 for left-sided tumors. The median number of N2 nodes harvested was 11 on the right and 12 on the left. A median of at least six nodes was harvested from at least three stations in 99% of patients, and 90% of patients had at least 10 nodes harvested from three stations. Overall, 21 patients (4%) were found to have occult N2 disease.Although high variability exists in the actual number of lymph nodes obtained from various nodal stations, complete mediastinal lymphadenectomy removes one or more lymph nodes from all mediastinal stations. Adequate mediastinal lymphadenectomy should include stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4L, 5, 6, 7, 8, and 9 for left-sided cancers. Six or more nodes were resected in 99% of patients in this study.ClinicalTrials.gov; No.: NCT00003831; URL: clinicaltrials.gov.
Project description:<b>Background:</b> Transbronchial needle aspiration (TBNA) is a classical technique for diagnosing mediastinal-hilar lymph node enlargement. However, the diagnostic value of conventional TBNA (cTBNA) is limited in small lymph nodes. <b>Methods:</b> Here, we generated an innovative multi-dimensional virtual lymph node map on top of Wang's lymph node map using a Lungpoint Virtual Bronchoscopic Navigation System. <b>Results:</b> The virtual bronchoscopic navigation (VBN) system was combined with computed tomography (CT) images to generate extrabronchial, endobronchial, sagittal, coronal as well as horizontal views of the 11 intrathoracic lymph node stations and their adjacent tissues and blood vessels. We displayed the specific puncture site of each lymph node station. The 11 stations were divided into four groups: right mediastinal stations, left mediastinal stations, central mediastinal stations and hilar stations. <b>Conclusion:</b> The VBN system provides a precise view of the intrabronchial landmarks, which may increase the diagnostic accuracy of intrathoracic lymph node adenopathy and assist bronchoscopists with practicing TBNA.
Project description:<h4>Background</h4>The role of upper mediastinal lymphadenectomy for distal esophageal or gastroesophageal junction (GEJ) adenocarcinomas remains a matter of debate. This systematic review aims to provide a comprehensive overview of evidence on the incidence of nodal metastases in the upper mediastinum following transthoracic esophagectomy for distal esophageal or GEJ adenocarcinoma.<h4>Methods</h4>A literature search was performed using Medline, Embase and Cochrane databases up to November 2020 to include studies on patients who underwent transthoracic esophagectomy with upper mediastinal lymphadenectomy for distal esophageal and/or GEJ adenocarcinoma. The primary endpoint was the incidence of metastatic nodes in the upper mediastinum based on pathological examination. Secondary endpoints were the definition of upper mediastinal lymphadenectomy, recurrent laryngeal nerve (RLN) palsy rate and survival.<h4>Results</h4>A total of 17 studies were included and the sample sizes ranged from 10-634 patients. Overall, the median incidence of upper mediastinal lymph node metastases was 10.0% (IQR 4.7-16.7). The incidences of upper mediastinal lymph node metastases were 8.3% in the 7 studies that included patients undergoing primary resection (IQR 2.0-16.6), 4,4% in the 1 study that provided neoadjuvant therapy to the full cohort, and 10.6% in the 9 studies that included patients undergoing esophagectomy either with or without neoadjuvant therapy (IQR 8.9-15.8%). Data on survival and RLN palsy rates were scarce and inconclusive.<h4>Conclusions</h4>The incidence of upper mediastinal lymph node metastases in distal esophageal adenocarcinoma is up to 10%. Morbidity should be weighed against potential impact on survival.
Project description:BACKGROUND:We sought to evaluate the safety and oncological efficacy of bilateral recurrent laryngeal nerve (RLN) lymph-node dissection (LND) in patients with esophageal squamous cell carcinoma (ESCC) who had undergone neoadjuvant chemoradiotherapy (nCRT). METHODS:We retrospectively examined the records of ESCC patients who were judged to be ycN-RLN(-) following nCRT. Patients were divided into two groups according to the extent of LND [standard two-field LND (STL group) versus total two-field LND (TTL group)]. Only lower mediastinal and upper abdominal lymph nodes were removed in the STL group. In addition to the standard procedure, patients in the TTL group underwent resection of upper mediastinal lymph nodes located along the bilateral RLN. Using propensity score matching, 29 pairs were identified and compared with regard to perioperative complications, lymph-node metastases rates, overall survival (OS), and disease-specific survival (DSS). RESULTS:No significant intergroup differences were identified in terms of in-hospital mortality and morbidity. Metastases to the RLN lymph nodes were identified in 20.7% (6/29) of TTL patients, being the only site of lymph-node metastases in three of them. TTL was associated with lower upper mediastinal lymph-node recurrence rate (6.5%) compared with STL (21.5%, p?=?0.134), although the overall recurrence rate was similar (STL, 44.8% versus TTL, 46.4%). No significant intergroup differences were also evident with regard to 3-year DSS and OS rates. CONCLUSIONS:RLN LND can be safely performed in ESCC patients who had undergone nCRT, ultimately resulting in an improved local control, and should be practiced as part of the surgical routine.
Project description:The differential diagnosis of progression and pseudoprogression is one difficulty in current immunotherapy. Since the time point and criteria for pseudoprogression diagnosis are not yet unified, current diagnosis and treatment rely on imaging and pathology. Here we report a 57-year-old Chinese male presented solitary left lower lung nodule with enlarged left hilar and mediastinal lymph nodes. Bilateral adrenal nodules and bilateral parietal lobe nodules were identified. The nodules were considered malignant by CT or MRI examinations. The patient was diagnosed left lower peripheral lung cancer with left hilar and mediastinal lymph node metastasis, bilateral adrenal metastasis, and bilateral parietal lobe metastasis. Progression was observed after the first-line pemetrexed + cisplatin (PP) standard chemotherapy. Due to the identification of strong positive PD-L1 expression (90%) in primary tissue immunohistochemistry, second-line IBI308 (sintilimab) immunotherapy was implemented. After the third cycle of immunotherapy, partial response was observed with the left lung lesion and the lung hilus and adrenal metastases, while pseudoprogression was found at the left lung and right hepatic lobe, and rare gingival progression was also identified. Palliative surgery was performed to remove the gingival metastatic lesion. The lesions of the lung, hilar and mediastinal lymph nodes and adrenal gland responded well, but the patient died due to uncontrollable progression of metastatic lesions in the brain. Whole-exome sequencing on gingival metastasis revealed pathogenic mutations in several important driver genes, including TP53, ErbB2, MET and PTEN. This study reported the coexistence of primary lesion response, pseudoprogression and progression in immunotherapy in lung cancer patient with rare gingival metastasis, and provided experience for handling mixed responses in immunotherapy.
Project description:BACKGROUND:Selection of the best lymph node for dissection is a controversial topic in clinical stage-I non-small cell lung cancer (NSCLC). Here, we sought to identify the clinicopathologic predictors of regional lymph node metastasis in patients intraoperatively diagnosed with stage-I NSCLC. METHODS:A retrospective review of 595 patients intraoperatively diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with complete lymph node dissection was performed. Univariate and multivariable logistic regression analysis was performed to determine the independent predictors of regional lymph node metastasis. RESULTS:Univariate logistic regression and multivariable analysis revealed three independent predictors of the presence of metastatic hilar lymph nodes, five independent predictors for lobe specific mediastinal lymph nodes, two independent predictors for lobe nonspecific mediastinal lymph nodes and two independent predictors for skipping mediastinal lymph nodes. CONCLUSIONS:A complete mediastinal lymph node dissection may be considered for patients suspected of nerve invasion and albumin (>?43.1?g/L) or nerve and vascular invasions. Lobe-specific lymph node dissection should probably be performed for patients suspected of pulmonary membrane invasion, vascular invasion, CEA (>?2.21?ng/mL), and tumor (>?1.6?cm) in the right lower lobe or mixed lobes. Hilar lymph node dissection should probably be performed for patients suspected of having bronchial mucosa and cartilage invasion, vascular invasion, and CEA (>?2.21?ng/mL).