Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

Relationship Between Breast Density,Breast Cancer Subtypes,and Prognosis

BackgroundIn the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women.Patients and MethodsBetween 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated.ResultsNo significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types.ConclusionThere was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.     

Stromal characteristics are adequate prognosticators for recurrence risk in ductal carcinoma in situ of the breast

BackgroundDuctal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of non-obligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence. In the present study, we investigated the prognostic potential of stromal characteristics.MethodsHematoxylin and eosin stained slides from 211 DCIS patients were reviewed. The following histological features were dichotomously assessed: nuclear grade, DCIS architecture, presence of necrosis, intraductal calcifications, stromal inflammation and myxoid stromal architecture. Loco-regional recurrences constituted the primary endpoint. Results: Cox regression analysis showed that high nuclear grade, myxoid stromal architecture and moderate to extensive stromal inflammation were significantly associated with decreased recurrence-free survival, independent of radiotherapy. Based on these features, a combined risk score (CRS) was calculated, ranging from zero to three. A high CRS of three was associated with significantly shorter recurrence-free survival. Nineteen patients had a CRS of three, of which three relapsed (15.7%), whereas only one out of 113 patients with a CRS of zero relapsed (0.9%).ConclusionsWe were able to validate our previously reported findings regarding the prognostic potential of myxoid periductal stroma in an independent DCIS patient cohort. A CRS based on nuclear grade, myxoid stromal architecture and stromal inflammation might facilitate discrimination of low risk from high risk patients. Consequently, the CRS may tailor adjuvant therapy. Future research should investigate whether radiotherapy can be safely omitted in patients with a low CRS.     

Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer

IntroductionBreast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings.Material and methodsTissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry.ResultsTRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001).ConclusionEnhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.     

Risk factors for sexual dysfunction after rectal cancer surgery in 948 consecutive patients: A prospective cohort study

BackgroundSexual dysfunctions seriously affect the quality of life of patients. The aim of this study was to identify the risk factors for sexual dysfunction after rectal cancer surgery.MethodsA total of 948 consecutive patients undergoing rectal cancer radical resection were included between January 2012 and August 2019. The sexual functions were evaluated by the 5-item version of the International Index of Erectile Function (IIEF-5) in men and Index of Female Sexual Function (IFSF) in women at 12 months postoperatively.ResultsPostoperative sexual dysfunction was observed in 228 patients with rectal cancer (24.05%), which included 150 cases in male patients (25.0%) and 78 cases in female patients (22.5%). A multivariate logistic regression analysis results showed that age ≥45 years old (OR = 1.72, p = 0.001), tumor below the peritoneal reflection (OR = 1.64, p = 0.005), receiving preoperative radiotherapy (OR = 4.12, p < 0.001) and undergoing abdominoperineal resection (APR), intersphincteric resection (ISR) and Hartmann surgery (OR = 2.43, p < 0.001) were the independent risk factors of sexual dysfunction for patients with rectal cancer.ConclusionAge ≥45 years old, tumors below the peritoneal reflection, receiving preoperative radiotherapy, and undergoing APR, ISR and Hartmann surgery were the independent risk factors of sexual dysfunction. Patients should be informed about the sexual dysfunctions in the pre-operative consultations. More attention should be paid to intraoperative pelvic autonomic nerve preservation on rectal cancer patients with these risk factors for clinic surgeons.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

A novel MRI-based predictive index can identify patients suitable for preservation of the nipple-areola complex in breast reconstructive surgery

IntroductionAccurately predicting nipple-areola complex (NAC) involvement in breast cancer is necessary for identifying patients who may be candidates for a nipple-sparing mastectomy. Although multiple risk factors are indicated in the guidelines, it is difficult to predict NAC involvement (NAC-i) preoperatively even if these factors are evaluated individually. This study aimed to develop a more accurate and practical preoperative NAC-i prediction model using magnetic resonance imaging (MRI).Materials and methodsAll tumors in 252 patients were evaluated using postcontrast T1-weighted subtraction on MRI.ResultsThe receiver operating characteristic curves identified cut-off values for tumor size and tumor-to-nipple distance (TND) as 4 cm and 1.2 cm, respectively. Multivariate analysis demonstrated that TND (p < 0.001), ductal enhancement extending to the nipple (DEEN) (p < 0.001), and nipple enhancement (NE) (p = 0.005) were independent clinical risk factors for pathological NAC-i. A formula was constructed using odds ratios for these three independent preoperative risk factors in multivariate analysis: the MRI-based NAC-i predictive index (mNACPI) = TND × 4 + DEEN × 3 + NE × 1. A total score of ≤4 points was defined as low risk and ≥5 points as high risk. NAC-i rates were 2.4% in the low-risk group and 89.4% in the high-risk group; a significant correlation was observed between the risk group and permanent pathological NAC-i (p < 0.001). Assuming that the NAC was preserved in low-risk patients and resected in high-risk patients, NAC-i was verified using the mNACPI.ConclusionmNACPI may contribute greatly to the improvement of selecting suitable patients for NAC preservation in breast reconstructive surgery while maintaining oncological safety.     

A population-based study on incidence,treatment, and survival in ampullary cancer in the Netherlands

IntroductionAmpullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016.MethodsPatients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease.ResultsIn total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients.ConclusionBoth incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.     

A new method to optimize resection area using a radiation treatment planning system and deformable image registration for breast-conserving surgery after neoadjuvant chemotherapy

BackgroundWe devised a breast-conserving surgery (BCS) utilizing a new image-processing and projection technique using a radiation treatment planning system (RTPS) and deformable image registration (DIR) for patients with breast cancer after neoadjuvant chemotherapy (NAC). RTPSs and DIR are commonly used in planning radiation treatment. The purpose of this pilot study was to evaluate the feasibility of our procedure.Patients and methodsTwenty-six patients diagnosed with breast cancer underwent NAC and BCS between November 2014 and May 2020. Multidetector-row computed tomography was performed in the same position used for surgery before and after NAC. In the DIR, CT before NAC was fused to CT after NAC. The RTPS simulated the design of tumor excision, and excision area was projected onto the breast skin utilizing an irradiation device.ResultsIn 26 patients with breast cancer after NAC, BCS was performed using the processing and projection technique of the RTPS with DIR. Only 1 of 26 patients showed carcinoma present in the surgical margins, and subsequently developed ipsilateral breast tumor recurrence. Mean excised volume was 33.5 cm³ (range, 12.8–62.8 cm³), and percent breast volume excised was 6.8% (range, 2.5–15.7%).ConclusionsThis pilot study confirmed the simplicity and utility of our procedure for minimally invasive BCS in patients with breast cancer after NAC. We will keep evaluating the safety and efficacy of our procedure in more patients.     

New evidence supporting lung cancer screening with low dose CT & surgical implications

IntroductionLung cancer is the leading cause of cancer-death worldwide. The U.S. Preventative Services Task Force (USPTSF) approved screening for current or former smokers aged 55–80 based on the results of the National Lung Screening trial (NLST). Following the NLST, new evidence has emerged from clinical trials and updates to previous trials prior to the anticipated update to the USPSTF guideline. We review the new evidence on lung cancer screening with low dose computed tomography (LDCT) and the surgical implications.MethodsA review of new literature was performed pertaining to lung cancer screening since implementation of UPSTF guidelines. Articles for inclusion were identified by both authors’, then search of the Pubmed and Cochrane database was performed from January 1st, 2013 through February 4th, 2020 using the MeSH search terms: “lung cancer”; “screening”; “low dose CT”. The results of these studies are summarized.ResultsWe identified multiple prospective randomized control trials and meta-analysis since the NLST supporting lung cancer-specific mortality with screening. We identified new nodule classification systems and the development of risk-models which may reduce false positive rates and identify high risk patients not currently eligible for screening. Finally, we discussed the surgical implications of screening.ConclusionNew data supports NLST findings and show ongoing benefit to LDCT for lung cancer screening. Standardized LDCT screening classification has been shown to reduce harm and lower false positive rates. Further study is needed regarding use of risk-modeling. Screening will require an increase in the thoracic workforce to accommodate the amount of surgically operable cancers.     

Survival of surgical and non-surgical older patients with non-metastatic colorectal cancer: A population-based study in the Netherlands

BackgroundSurgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.ObjectiveTo examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.MethodsAll patients aged ≥70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.ResultsIn total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (≥80 years) did not decrease RS (colon; RER 0.9 (0.7–1.0), rectum; RER 0.9 (0.7–1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).ConclusionNon-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients.     

Breast cancer detection by dedicated breast positron emission tomography according to the World Health Organization classification of breast tumors

ObjectiveConsidering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET.MethodsA total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared.ResultsThe size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P < 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index.ConclusionsDBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.     

BCG Administration after Prior Radiation Treatment for Prostate Cancer

IntroductionProstate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. The underlying mechanism is incompletely understood but is thought to be related to an altered microenvironment promoting tumorigenesis. However, there is a gap in the literature regarding how the effect of BCG varies according to prior radiotherapy in patients with non–muscle invasive bladder cancer (NMIBC). In this context, we sought to evaluate oncologic outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy.MethodsThis is a retrospective cohort study that includes all patients who received intravesical for NMIBC at our institution from 2001 to 2019. Patients were stratified into 3 cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). The outcomes of interest were recurrence at 1-year, progression to muscle-invasive bladder cancer (MIBC), and progression to metastatic disease. Comparisons were also made between cohorts with respect to elapsed time from radiation therapy. Wilcoxon rank-sum test was used for comparing continuous variables, while χ² and Fischer's exact tests were used to examine categorical variables.ResultsIn 199 total patients who underwent BCG for NMIBC, 23 had a prior history of prostate radiotherapy treatment, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at 1 year. There was no difference in the number of induction or maintenance BCG administrations received between the cohorts within the first year. There was no significant difference in recurrence at 1 year between the 3 cohorts (P = .56). There was also no difference in progression to MIBC or progression to metastatic disease with P = .50 and 0.89, respectively.ConclusionThe risk of recurrence after induction BCG treatment for high-grade NMIBC does not vary according to prior radiation treatment for prostate cancer.     

Complications and risk factors in vulvar cancer surgery – A population-based study

IntroductionPrimary surgery for vulvar cancer has become less radical in past decades. This study investigates risk factors and prevalence of short-and long-term complications after up-to-date vulvar cancer surgery.MethodsPopulation-based cohort study of surgically treated primary vulvar cancer at a national center of vulvar cancer, assessing surgical outcome. The Swedish Quality Registry for Gynecological Cancer was used for identification, journals reviewed and surgical outcome including complications within 30 days and one year registered. Multivariable logistic regression analysis comprising risk factors of short-term complications; age>80 years, BMI, smoking, diabetes, lichen sclerosus and FIGO stage was performed.Results182 patients were identified, whereas 55 had vulvar surgery only, 53 surgery including sentinel lymph node biopsy (SLNB) and 72 surgery including inguinofemoral lymphadenectomy (IFL), with short-term complication rates of 21.8%, 39.6% and 54.2% respectively. Vulvar wound dehiscence was reported in 6.0% and infection in 13.7%. Complication rates were lower after SLNB than IFL (wound dehiscence 0% vs 8.3%; p = 0.04, infection 15.1% vs 36.1%; p = 0.01 and lymphocele 5.7% vs 9.7%; p = 0.52). Severe complications were rare. Persisting lymphedema evolved in 3.8% after SLNB and in 38.6% after IFL (p = 0.001), ubiquitous after adjuvant radiotherapy. In multivariable regression analysis, no associations between included risk factors and complications were found.ConclusionSurgical complications are still common in vulvar cancer surgery and increase with the extent of groin surgery. To thrive for early diagnosis and to avoid IFL seem to be the most important factors in minimizing short-and long-term complications.     

Geriatric Early-Stage Triple-Negative Breast Cancer Patients in Low-risk Population: Omitting Chemotherapy Based on Nomogram

BackgroundConsidering old age and comorbidities, the actual benefit of chemotherapy in older patients with early triple-negative breast cancer (TNBC) remains uncertain. We aimed to select appropriate patients who could avoid chemotherapy in this population.MethodsA total of 6482 patients more than 65 years old with T1-2N0-1M0 TNBC in 2010-2015 were extracted from SEER program. Multivariate logistic regression was performed to identify independent factors associated with chemotherapy usage. Survival analysis was performed using Kaplan-Meier plots and log-rank tests. Independent prognostic factors were identified by multivariate Cox analysis. A nomogram predicting breast cancer-specific survival (BCSS) and a risk stratification model were constructed.ResultsA total of 3379 (52.13%) patients received chemotherapy while 3103 (47.87%) did not. Age, married status, grade, T-stage, N-stage, radiation and breast-conserving surgery (BCS) were significantly associated with chemotherapy usage (all P < .05). Chemotherapy significantly improved OS (HR = 0.606, P < .001) and BCSS (HR = 0.763, P = .006) in the entire population. A nomogram was built by incorporating independent risk factors (age, T-stage, N-stage, grade and radiation). Based on the score of the nomogram, the risk stratification model demonstrated that chemotherapy improved OS (P < .001) and BCSS (P < .001) of patients in the high-risk group (score >180), but not in the low-risk group (score ≤75).ConclusionChemotherapy is beneficial for geriatric patients with T1-2N0-1M0 TNBC in this study, and the risk stratification model indicates the feasibility of sparing chemotherapy in low-risk subgroup without sacrificing survival, providing clinicians tools to weigh the risk–benefit of chemotherapy and customize the individualized treatment accordingly.     

HER2 as a potential biomarker guiding adjuvant chemotherapy in stage II colorectal cancer

BackgroundHER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy.MethodsWe analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II colon cancer patients. We further validated the finding by retrospectively analyzing HER2 detection of immunohistochemistry in a cohort of 282 patients in Fudan University Shanghai Cancer Center (FUSCC).ResultsIn GSE39582 dataset, chemo-treated HER2-high patients had a better overall survival (OS) and relapse-free survival (RFS) versus chemo-naïve HER2-high patients (5-year OS: 100% vs 69.5%, 5-year RFS: 100% and vs 64%, P = 0.027 and 0.025, respectively). On the contrary, chemo-treated HER2-low patients had a worse RFS compared with chemo-naïve HER2-low patients (5-year RFS: 65.6% vs 82.1%, P = 0.022). In FUSCC cohort, chemo-treated HER2-positive patients exhibited better OS vs chemo-naïve HER2-positive patients (5-year OS: 100% vs 73.8%, P < 0.001), and showed marginal evidence of a lower probability of recurrence (5-year RFS: 74.4% vs 58.7%, P = 0.072). After stratifying by mismatch repair (MMR) status, the results only kept consistency in patients with pMMR status.ConclusionsHER2-positve patients with stage II colorectal cancer can benefit from 5-fluorouracial based adjuvant chemotherapy, especially for patients with pMMR status.     

Can physical prehabilitation prevent complications after colorectal cancer surgery in frail older patients?

IntroductionFrail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated the effect of physical prehabilitation on postoperative complications in a retrospective cohort of frail CRC patients.MethodsThe study consisted of all consecutive non-metastatic CRC patients ≥70 years who had elective surgery from 2014 to 2019 in a teaching hospital in the Netherlands, where a physical prehabilitation program was implemented from 2014 on. We performed both an intention-to-treat and per protocol analysis to evaluate postoperative complications in the physical prehabilitation (PhP) and non-prehabilitation (NP) group.ResultsEventually, 334 elective patients were included. The 124 (37.1%) patients in the PhP-group presented with higher age, higher comorbidity scores and walking-aid use compared to the NP-group. Medical complications occurred in 26.6% of the PhP-group and in 20.5% of the NP-group (p = 0.20) and surgical complications in 19.4% and 14.3% (p = 0.22) respectively. In all frailty subgroups, the medical complications were lower in the PhP-group compared to the NP-group (35.9% vs. 45.5% for patients with ≥2 comorbidities, 36.2% vs. 39.1% for ASA score ≥ III, 29.2% vs. 45.8% for walking-aid use). Differences were not significant.ConclusionsIn this study, patients selected for physical prehabilitation had a worse frailty profile and therefore a higher a priori risk of postoperative complications. However, the postoperative complication rate was not increased compared to patients who were less frail at baseline and without prehabilitation. Hence, physical prehabilitation may prevent postoperative complications in frail CRC patients ≥70 years.     

Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients.     

Myosteatosis predicts higher complications and reduced overall survival following radical oesophageal and gastric cancer surgery

IntroductionLow muscle attenuation, as governed by increased intramuscular fat infiltration (myosteatosis), may associate with adverse surgical outcomes. We aimed to determine whether myosteatosis is associated with an increased risk of postoperative complications and reduced long-term survival after oesophago-gastric (OG) cancer surgery.MethodsPatients who underwent radical OG cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Myosteatosis was evaluated using previously defined cut-points for low skeletal muscle attenuation measured by CT. Oncological, surgical, complications, and outcome data were obtained from a prospective database.ResultsOf 108 patients, 56% (n = 61) had myosteatosis. Patients with myosteatosis were older (69.1 ± 9.1 vs. 62.8 ± 9.8 years, p = 0.001) and had a similar body mass index (BMI) (23.4 ± 5.3 vs. 25.9 ± 6.7 kg/m², p = 0.766) compared to patients with normal muscle attenuation. Patients with myosteatosis had a higher rate of anastomotic leaks (15% vs. 2%, p = 0.041). On multivariate analysis, myosteatosis was an independent predictor of overall (OR 3.03, 95% CI 1.31–6.99, p = 0.009) and severe complications (OR 4.33, 95% CI 1.26–14.9, p = 0.020). Patients with myosteatosis had reduced 5 year overall (54.1% vs. 83%, p = 0.004) and disease-free (55.2% vs. 87.2%, p = 0.007) survival.ConclusionMyosteatosis is associated with a significantly increased risk of overall and severe complications as well as substantially reduced long-term survival. Assessment of muscle attenuation provides analysis beyond standard anthropometrics and may form part of preoperative physiological staging tools used to improve surgical outcomes.     

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study

BackgroundTrifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.MethodsFrom October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with bevacizumab or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.ResultsA total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, P = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, P = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, P = .013). Patients without prior regorafenib or fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, P = .031) and OS (NR vs. 9.0 m, P = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.ConclusionIn real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.