How we treat esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) poses a major challenge for clinicians as the prognosis is poor and treatment options are limited. However, recent advances in immunotherapy have significantly changed the treatment algorithm of ESCC. Patients with early ESCC should undergo an endoscopic resection. If histological margins are infiltrated with tumor cells or other risk factors for lymph node metastasis are present, further resective surgery should be offered. In a locally advanced setting, radiochemotherapy with or without resection remains the standard of care. In the absence of pathological complete response after neoadjuvant radiochemotherapy and R0 resection, adjuvant immunotherapy for 1 year should be administered to improve disease-free survival. In metastatic first-line setting, combination of platin/fluoropyrimidine-based systemic chemotherapy with checkpoint inhibitors is the novel standard of care for all-comers in the United States and for patients with programmed death-ligand 1 positivity in Europe. Immunotherapy has also been approved in a second-line setting. However, the benefit from immunotherapy reinduction is still unknown and, therefore, standard second-line chemotherapy with taxanes or irinotecan is still the treatment of choice after progression on immunochemotherapy. It is of highest importance that treatment decisions are based on informed patient wishes and are discussed in an interdisciplinary tumor board. This review summarizes how to manage, in our opinion, patients with ESCC and gives a practical overview of the treatment strategies in Europe.

Development of an alarm symptom-based risk prediction score for localized oesophagogastric adenocarcinoma (VIOLA score).

BACKGROUND: Gastroesophageal adenocarcinoma is a major contributor to global disease burden with poor prognosis even in resectable, regionally limited stages. Feasible prognostic tools are crucial to improve patient management, yet scarce. PATIENTS AND METHODS: Disease-related symptoms, patient, tumour, treatment as well as laboratory parameters at initial diagnosis and overall survival (OS) of patients with stage II and III gastroesophageal adenocarcinoma, who were treated between 1990 and 2020 at the Medical University of Vienna, were evaluated in a cross-validation model to develop a feasible risk prediction score. RESULTS: In total, 628 patients were included in this single-centre analysis. The final score ranked from 0 to 10 and included the factors sex (female +1), age, years (30-59 +1, >60 +2), underweight classified by body mass index (+2), location of the tumour (stomach +1), stage (III +2), stenosis in endoscopy (+1) and weight loss (+1). The score was grouped into low- (0-3), medium- (4-6) and high-risk (7+) subgroups. The median OS were 70.3 [95% confidence interval (CI) 51.2-111.8], 23.4 (95% CI 21.2-26.7) and 12.6 (7.0-16.1) months, respectively. The 1-year survival probabilities were 0.88 (95% CI 0.83-0.93), 0.75 (95% CI 0.70-0.79) and 0.54 (95% CI 0.39-0.74), whereas the 5-year survival probabilities were 0.57 (95% CI 0.49-0.66), 0.24 (95% CI 0.20-0.28) and 0.09 (95% CI 0.03-0.28), respectively. CONCLUSIONS: The VIennese risk prediction score for Oesophagogastric Localized Adenocarcinoma (VIOLA) risk prediction score poses a feasible tool for the estimation of OS in patients with regionally limited gastroesophageal adenocarcinoma and, thus, may improve patient management in clinical routine. Prospective analyses should be carried out to confirm our findings.

Correlation of trastuzumab-based treatment with clinical characteristics and prognosis in HER2-positive gastric and gastroesophageal junction cancer: A retrospective single center analysis.

Attempts for identifying targeted therapy strategies in metastatic gastric and gastroesopheal junction cancer (upper-GI) revealed that the inhibition of human epidermal growth factor receptor-2 (HER2) by monoclonal antibody trastuzumab improves survival of these patients. Hence, adding trastuzumab to doublet chemotherapy has become the standard treatment in this setting. Although the patient survival is extended among clinical trials, the knowledge on the real-time setting is limited. With this retrospective, single center analysis of the patient data of the Medical University of Vienna, we sought to investigate the clinical characteristics and outcome of patients, who received trastuzumab-based chemotherapy for metastatic upper-GI tumor. All patients, who received trastzumab at least once were included to the analysis. Clinical and pathological data were recorded. This search revealed 33 patients. The demographic data was comparable with that of the previous clinical trials. Progression free survival (PFS) was 11 months, whereas overall survival (OS) was 21 months. OS was significantly associated with initially favorable response to treatment. Thirteen patients (39%) received trastuzumab as maintenance treatment with a median cycle number of 6. Toxicity profile was acceptable with only one patient detected to have cardiotoxicity. Taken together, trastuzumab based treatment induced a considerable PFS and OS in metastatic or advanced upper-GI tumors with acceptable toxicity profile. The maintenance therapy with trastuzumab was safe and effective in patients who had initially a favorable response to chemotherapy. The optimal duration of the maintenance therapy should be tested in future clinical trials.

Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases.

BACKGROUND: Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. METHODS: Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. RESULTS: NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0%) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5%) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. CONCLUSION: Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies.

Brain-only metastatic breast cancer is a distinct clinical entity characterised by favourable median overall survival time and a high rate of long-term survivors.

BACKGROUND: The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored. METHODS: All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed. RESULTS: In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001). CONCLUSIONS: Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.