Increasing opportunities for breast-conserving therapy in multiple ipsilateral breast cancer: Dutch nationwide study.

INTRODUCTION: An increasing number of breast cancer patients undergo breast-conserving surgery (BCS), but multiple ipsilateral breast cancer (MIBC) is still considered a relative contraindication for breast conservation. This study provides an update on trends in the surgical management for MIBC over a 10-year period. METHODS: Nationwide data from the Netherlands Cancer Registration of all patients diagnosed with breast cancer between 2011 and 2021 were analysed. The primary outcomes of this study were the incidence of MIBC and the trend in breast surgery type among patients between 2011 and 2021. Secondary outcomes were the positive resection margin rates in patients treated with BCS, the proportion of patients requiring re-excision and overall survival. RESULTS: In total, 114 433 patients (83%) with unifocal breast cancer and 23 932 patients (17%) with MIBC were identified. The incidence of MIBC was stable (17%) over the years. Overall BCS rates, both primary and after neoadjuvant chemotherapy, increased in MIBC from 29% in 2011 to 41% in 2021. Re-excision was performed in 1348 patients (n = 8455, 16%). The 5-year OS estimate for patients with MIBC treated with BCS was 93%. The pathological complete response (pCR) in MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy was 23%. CONCLUSION: The breast conservation rate in MIBC has increased over the last decade. In addition, 23% of MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy achieved a pCR. This suggests increasing opportunities for even more BCS in MIBC.

Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a high mortality neoplasm which usually appears on a cirrhotic liver. The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis. Notwithstanding the current deployment of treatments with curative intent (liver resection/local ablation and liver transplantation) in early and intermediate stages, a high rate of HCC recurrence persists, underscoring a pivotal clinical challenge. Emergent systemic therapies (ST), particularly immunotherapy, have demonstrate promising outcomes in terms of increase overall survival, but they are currently bound to the advanced stage of HCC. This review provides a comprehensive analysis of the literature, encompassing studies up to March 10, 2024, evaluating the impact of novel ST in the early and intermediate HCC stages, specially focusing on the findings of neoadjuvant and adjuvant regimens, aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent. We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent. Finally, we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Operative trends for pancreatic and hepatic malignancies during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted routine health care, including many elective and non-cancer operations in the United States. Most hepato-pancreato-biliary malignancy patients require outpatient imaging, tissue sampling, and staging, and many undergo neoadjuvant therapy before operative intervention. The aims of this study were to evaluate the effect of the COVID-19 pandemic on hepato-pancreato-biliary oncologic operations and to determine whether trends in neoadjuvant therapy were altered by the pandemic. METHODS: Adult patients in the United States undergoing oncologic operations for pancreatic, primary and secondary hepatic malignancies, with or without neoadjuvant therapy, were extracted from the Vizient Clinical Data Base. Control chart analysis was used to plot trends over time and to determine whether changes were statistically significant. Wilcoxon rank-sum tests also compared monthly operative volume from pre-pandemic (12 month) and pandemic (28 months) periods. RESULTS: A total of 36,553 patients were identified over 40 months. Mean monthly pancreatic oncologic operations were unaffected by the pandemic (P = .257). Operations for pancreatic oncologic operations with prior neoadjuvant therapy increased throughout the pandemic (P = .002). Oncologic operations for primary and secondary hepatic malignancies were significantly reduced for 4 and 2 months, respectively, at the beginning of the pandemic but returned to their pre-pandemic baseline within 4 months (P = .169 and P = .598). CONCLUSION: Pancreatic operation volumes for cancer did not change, but pancreatic operations after neoadjuvant therapy continued to increase during the pandemic. Operations for hepatic malignancy were transiently disrupted but quickly normalized. These observations suggest that surgery for hepato-pancreato-biliary malignancies was prioritized during the pandemic.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.

OBJECTIVE: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. METHODS: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). RESULTS: We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). CONCLUSIONS: The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.

The "collateral damage" of the war on COVID-19: impact of the pandemic on the care of epithelial ovarian cancer.

The covid-19 pandemic has impacted the management of non-covid-19 illnesses. Epithelial ovarian cancer (EOC) requires long-duration multidisciplinary treatment. Teleconsultation and shared care are suggested solutions to mitigate the consequences of the pandemic. However, these may be challenging to implement among patients who come from the lower economic strata. We report the disastrous impact of the pandemic on the care of EOC by comparing patients who were treated during the pandemic with those treated in the previous year. We collected the following data from newly diagnosed patients with EOC: time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients completing various components of therapy (surgery and chemotherapy). Patients treated between January 2019 and September 2019 (Group 1: Pre-covid) were compared with those treated between January 2020 and December 2020 (Group 2: During covid pandemic). A total of 82 patients were registered [Group 1: 43(51%) Group 2: 39(49)]. The median time from diagnosis to start of treatment was longer in group 2 when compared to group 1 [31(23-58) days versus 17(11-30) days (p = 0.03)]. The proportion of patients who had surgery in group 2 was lower in comparison to group 1 [33(77%) versus 21(54%) (p = 0.02)]. Proportion of patients who underwent neoadjuvant (NACT) and surgery were fewer in group 2 in comparison to group 1 [9(33%) versus 18(64%) p = 0.002]. Among patients planned for adjuvant chemotherapy, the median time from diagnosis to treatment was longer in group 2 [28(17-45) days, group 1 versus 49(26-78) days, group 2 (p = 0.04)]. The treatment of patients with EOC was adversely impacted due to the COVID-19 pandemic. There was a compromise in the proportion of patients completing planned therapy. Even among those who completed the treatment, there were considerable delays when compared with the pre-covid period. The impact of these compromises on the outcomes will be known with longer follow-up.

Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives.

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Breast cancer immunotherapy: Current and novel approaches.

The crucial role of the immune system in the progression/regression of breast cancer (BC) should always be taken into account. Various immunotherapy approaches have been investigated for BC, including tumor-targeting antibodies (bispecific antibodies), adoptive T cell therapy, vaccines, and immune checkpoint blockade such as anti-PD-1. In addition, a combination of conventional chemotherapy and immunotherapy approaches contributes to improving patients' overall survival rates. Although encouraging outcomes have been reported in most clinical trials of immunotherapy, some obstacles should still be resolved in this regard. Recently, personalized immunotherapy has been proposed as a potential complementary medicine with immunotherapy and chemotherapy for overcoming BC. Accordingly, this review discusses the brief association of these methods and future directions in BC immunotherapy.

Current trends in the treatment of HR+/HER2+ breast cancer.

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.

Trends in the treatment of pancreatic cancer in Japan.

Pancreatic cancer is known to have the poorest prognosis among digestive cancers. With the development of new chemotherapeutic agents and introduction of multidisciplinary therapy, however, the treatment outcomes for pancreatic cancer have dramatically improved over the past two decades. The keys to successful treatment will be accurate assessment of resectability [resectable (R), borderline resectable (BR) or unresectable (UR)] at the time of diagnosis and prompt adoption of an appropriate multidisciplinary treatment strategy. Prep-02/JSAP-05 trial which is an RCT of upfront surgery versus neoadjuvant chemotherapy using GEM and S-1 (GS) and subsequent surgery for R-PDAC in Japan indicated neoadjuvant chemotherapy had a longer overall survival (OS) than those undergoing upfront surgery (36.7M vs. 26.6M, p = 0.015). In a retrospective multicenter study in Japan reported that in BR-PDAC, median survival time (MST) in the pretreatment group was significantly better than that in the upfront surgery group (25.7 months vs. 19.0 months, p = 0.015) according to a propensity score matching analysis. Another retrospective multicenter study with UR-LA PDAC in Japan reported that conversion surgery was more beneficial for patients with more than 8 months of preoperative therapy than those with less than 8 months of that therapy. Various clinical trials on pancreatic cancer are ongoing, and the results of trials on chemotherapeutic regimens and multidisciplinary treatments will be of further interest.

Persistent High Rate of Positive Margins and Postoperative Complications After Surgery for cT4 Rectal Cancer at a National Level.

BACKGROUND: A more extensive resection is often required in locally advanced rectal cancer, depending on preoperative neoadjuvant treatment response. OBJECTIVE: Circumferential margin involvement and postoperative outcomes after total mesorectal excision and multivisceral resection were assessed in patients with clinical locally advanced (cT4) rectal cancer at a national level. DESIGN: This is a population-based study. SETTINGS: Data were retrieved from the Dutch Colorectal Audit. PATIENTS: A total of 2242 of 2881 patients with cT4 rectal cancer between January 2009 and December 2017 were selected. MAIN OUTCOME MEASURES: Main outcomes were resection margins, postoperative complications, and mortality. RESULTS: Multivisceral resection was performed in 936 of 2242 patients, of whom 629 underwent extended multivisceral resection. Positive circumferential margin rate was higher after multivisceral resection than after total mesorectal excision: 21.2% vs 13.9% (p < 0.001). More postoperative complications occurred after limited and extended multivisceral resections than after total mesorectal excision (44.1% and 53.8% vs 37.6%, p < 0.001). Incidence of 30-day mortality was similarly low in both groups (1.5% vs 2.2%, p = 0.20). Independent predictors of postoperative complications were age ≥70 years (OR, 1.28 [95% CI, 1.04-1.56]; p = 0.02), male sex (OR, 1.68 [95% CI, 1.38-2.04]; p< 0.001), mucinous tumors (OR, 1.55 [95% CI, 1.06-2.27]; p = 0.02), extended multivisceral resection (OR, 1.98 [95% CI, 1.56-2.52]; p< 0.001), Hartmann procedure (OR, 1.42 [95% CI, 1.07-1.90]; p = 0.02), and abdominoperineal resection (OR, 1.56 [95% CI, 1.25-1.96]; p < 0.001). LIMITATIONS: Data specifying the extent of multivisceral resections and Clavien Dindo I to II complications were not available. CONCLUSIONS: This population-based study revealed relatively high circumferential margin positivity and postoperative complication rates in patients with cT4 rectal cancer, especially after multivisceral resections, but low mortality rates. See Video Abstract at http://links.lww.com/DCR/B457. ALTA TASA PERSISTENTE DE MRGENES POSITIVOS Y COMPLICACIONES POSTOPERATORIAS DESPUS DE LA CIRUGA DE CNCER RECTAL CTA NIVEL NACIONAL: ANTECEDENTES:A menudo se requiere una resección más extensa en el cáncer de recto localmente avanzado, según la respuesta al tratamiento neoadyuvante preoperatorio.OBJETIVO:Se evaluó la afectación del margen circunferencial y los resultados postoperatorios después de la escisión mesorrectal total y la resección multivisceral en pacientes con cáncer rectal clínico localmente avanzado (cT4) a nivel nacional.DISEÑO:Este es un estudio poblacional.ENTORNO CLINICO:Los datos se recuperaron de la Auditoría colorrectal holandesa.PACIENTES:Se seleccionaron un total de 2242 de 2881 pacientes con cáncer de recto cT4 entre enero de 2009 y diciembre de 2017.PRINCIPALES MEDIDAS DE VALORACION:Los principales resultados fueron los márgenes de resección, las complicaciones postoperatorias y la mortalidad.RESULTADOS:Se realizó resección multivisceral en 936 de 2242 pacientes, de los cuales 629 fueron sometidos a resección multivisceral extendida. La tasa de margen circunferencial positivo fue mayor después de la resección multivisceral que después de la escisión mesorrectal total: 21,2% versus a 13,9% (p <0,001). Se produjeron más complicaciones postoperatorias después de resecciones multiviscerales limitadas y extendidas en comparación con la escisión mesorrectal total (44,1% y 53,8% versus a 37,6%, p <0,001). La incidencia de mortalidad a 30 días fue igualmente baja en ambos grupos (1,5% versus a 2,2%, p = 0,20). Los predictores independientes de complicaciones posoperatorias fueron la edad ≥70 años (OR = 1,28, IC del 95% [1,04 a 1,56], p = 0,02), hombres (OR = 1,68, IC del 95% [1,38 a 2,04], p <0,001), tumores mucinosos (OR = 1,55, IC del 95% [1,06 a 2,27], p = 0,02), resección multivisceral extendida (OR = 1,98, IC del 95% [1,56 a 2,52], p <0,001), Hartmann (OR = 1,42, 95% Cl [1,07 a 1,90], p = 0,02) y resección abdominoperineal (OR 1,56, Cl 95% [1,25 a 1,96], p <0,001).LIMITACIONES:No se disponía de datos que especificaran el alcance de las resecciones multiviscerales y las complicaciones de Clavien Dindo I-II.CONCLUSIONES:Este estudio poblacional reveló tasas de complicaciones postoperatorias y positividad del margen circunferencial relativamente altas en pacientes con cáncer de recto cT4, especialmente después de resecciones multiviscerales, pero tasas de mortalidad bajas. Consulte Video Resumen en http://links.lww.com/DCR/B457.

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high-risk upper tract urothelial carcinoma: a multicentre retrospective study.

OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Use of treatment pathway improves neoadjuvant chemotherapy use in muscle-invasive bladder cancer.

PURPOSE: To assess the trends of neoadjuvant chemotherapy (NAC) use since its introduction in our practice pathway in patients with cT2 + bladder cancer over a 20-year period. METHODS: This is a retrospective review of patients with cT2 + bladder cancer who underwent RC between 01/01/1998 and 01/01/2018 that aimed to evaluate the trends of NAC use and associated after implementation of a multidisciplinary treatment pathway. Cohorts were stratified into eras: pre-NAC (1998-2007) to NAC eras (2008-2018). Univariate analysis was conducted using Chi-squared test and Kaplan-Meier estimates were used to evaluate survival. RESULTS: In 904 total patients who underwent RC, there were 493 with cT2 + UCC disease. The rate of NAC peaked at 84.2% in the most recent year of analysis in all patients and was 100% in cT2 + patients eligible for NAC. There was an increased rate of complete response (downstage to pT0) from 8.7% to 15.8% (p = 0.018) between the two eras. Unadjusted survival analysis revealed improved overall survival (OS) between eras with 5-year OS 53.2% vs. 42.7% and 10-year OS 42.7% vs. 26.4% in the NAC vs. pre-NAC cohorts, respectively (p = 0.016). CONCLUSIONS: In this review of 20 years of experience, we report a dramatic rise in the use of NAC after adoption of a multidisciplinary pathway that is associated with expected survival benefits.

Current advancements and future perspectives of immunotherapy in colorectal cancer research.

5-Fluorouracil (5-FU) is the first-line chemotherapy drug for colorectal cancer but most of the patients get resistant to the drug on a longer course of treatment. After the successful use of immunotherapy in melanoma treatment, it was explored with enthusiasm in different types of solid cancers including colorectal cancer. Nivolumab and pembrolizumab (Programmed cell death-1 blocking antibodies) have shown efficacy in the mismatch repair deficient high microsatellite instability (dMMR-MSI-H) subtype of metastatic colorectal cancer (CRC) patients. Immunotherapy has shown long time remission in a subset of metastatic CRC patients. The molecular mechanism and emerging roles of immunotherapy in colorectal cancer are explored in this review article and future directions for the proper utilization of the development in immunobiology are suggested.

A nine-lncRNA signature predicts distant relapse-free survival of HER2-negative breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy.

Multi-gene prognostic signatures of long non-coding RNAs (lncRNAs) provide new insights into mechanisms of HER2-negative breast cancer development and progression, and predict distant relapse-free survival (DRFS) of patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. The aim of this study was to develop such a multi-lncRNAs signature. Optimal multiple candidate signature lncRNAs associated with DRFS were firstly identified by a univariate Cox proportional hazard regression survival analysis and a robust likelihood-based survival analysis of the GEO dataset GSE25055. A nine-lncRNA prognostic risk score model Risk Score = 0.0289 × EXPLOC100507388 - 0.0814 × EXPLINC00094 - 0.2422 × EXPSMG7-AS1 - 0.2433 × EXPPP14571 + 0.4690 × EXPASAP1-IT1 - 0.2483 × EXPLOC103344931 - 0.2464 × EXPFAM182A + 0.3349 × EXPHCG26 - 0.0216 × EXPLINC00963 was built according to the coefficients of multivariate survival analysis of the association between the candidate lncRNAs and survival. EXPlncRNA was the standardized log2-transformed expression level of the gene. According to this model, higher scores predicted lower survival probability. The area under Receiver operating characteristic (ROC) curve (AUC) was 0.777 to 0.823 from 1- to 7- year survival rate. The model and its individual lncRNAs differentiated survival probability between the higher scores (expression) and the lower scores (expression). The nine-lncRNA signature had the robust prognostic power compared with ER, PR, tumor size (T), lymph node invasion (N), TNM stage, pathologic response, chemosensitivity prediction and PAM50 signature. These results were consistent with those based on the GEO dataset GSE25065. The predictive nomograms integrating both the nine-lncRNA signature classifier and clinical-pathological risk factors were robust in predicting 1-, 3- and 5- year survival probabilities. These results supported that the nine-lncRNA signature was a robust and effective model in predicting DRFS of patients with HER2-negative breast cancer following taxane and anthracycline-based neoadjuvant chemotherapy.