Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Implementation of a Telechemotherapy Module in the Peruvian Jungle with Adequate Quality of Life:Breaking the Access Gaps to Health with Teleoncology

Background: Cancer is a leading cause of death worldwide as well as in Peru. The national cancer plan includes decentralization, but one of the greatest barriers is our complicated geography. San Martin is a department located in the Peruvian jungle where there are no public services for cancer care. Our aim was to implement a “distance telemedicine-enabled” outpatient chemotherapy module, monitored by oncologists. Methods: The implementation was conducted in 3 stages: 1) Planning and Organization: working teams were formed, a chemotherapy room was developed and people were trained. 2) Execution: patients from San Martín region, aged >18 years with pathological confirmation of cancer, requiring systemic chemotherapy, ECOG <3, and first course of chemotherapy received at INEN without adverse reaction were selected. 3) Evaluation: adverse events, cost-user evaluation and quality of life (QoL) were assessed. Results: By November 2015, a module with a chemotherapy room with 18 chairs, a pharmacy, a hospitalization room, 1 medical office, a training room, a nutrition area, and a nursing station was implemented. 3 physicians, 3 nurses and 1 pharmacist were trained. Through March 2018, 501 sessions of teleoncology were completed to deliver 232 cycles of chemotherapy for 56 patients aged 19 - 78 years with different solid tumors, with no serious adverse event, without negatively affecting their QoL, and with an average out-of-pocket expense saving of 500 PEN. Conclusions: Using information and communication technology, a telechemotherapy module was successfully implemented in the Peruvian jungle, without adversely affecting the QoL of patients. Neither patients nor family members needed to travel to Lima to receive chemotherapy. This first program can be replicated in other rural and remote regions through non-specialized personnel and facilities, providing chemotherapy services equivalent to a tertiary center through trained health care professionals, supported through telemedicine.

Immunotherapy in triple-negative breast cancer:A literature review and new advances

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment options.It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment.Immunotherapy has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected populations.In this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

A biomarker study in Peruvian males with breast cancer

BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.AIM To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population.METHODS This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018.Standard pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material.Percentage of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide scanning.Statistical analyses included association tests,intraclass correlation test and Kaplan Meier overall survival curves.RESULTS The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast tumors.Median TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher grade.AR-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,P<0.001).Loss of MMR proteins was found in 15.4%and PIK3CA mutation(H1047R)in 14.3%(belonged to the Luminal-A phenotype).Loss of MMR proteins was associated with AR-negative(P=0.018)but not with ER(P=0.43)or TIL(P=0.84).Early stages(P<0.001)and lower grade(P=0.006)were associated with longer overall survival.ER status,phenotype,AR status,TIL level,MMR protein loss nor PIK3CA mutation was not associated with survival(P>0.05).CONCLUSION Male BC is usually ER and AR positive,and Luminal-A.MMR loss and PIK3CA mutations are infrequent.Stage and grade predicted overall survival in our South American country population.