Definitive concurrent chemoradiotherapy with paclitaxel plus carboplatin is superior to cisplatin plus 5-fluorouracil in patients with inoperable esophageal squamous cell carcinoma using retrospective, real-world evidence.

BACKGROUND: The optimal definitive chemotherapy regimen during concurrent chemoradiotherapy (CRT) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of conflicting evidence. This study aimed to compare the effectiveness of taxane-based chemotherapy with that of conventional cisplatin plus 5-fluorouracil (PF) as the chemotherapy regimen in definitive CRT for ESCC. PATIENTS AND METHODS: This retrospective study included patients with ESCC who received paclitaxel plus carboplatin (PC) or PF during definitive CRT between May 2012 and February 2015 in a medical center in Taiwan. Survival outcomes were compared after adjustment for risk factors. RESULTS: Overall, 229 patients were evaluated. Patients in the PC group had an objective response rate of 71.1% compared with the 51.4% of the PF group (p = 0.016). The PC group showed a significantly longer progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.019) than the PF group. Salvage surgery also helped prolong both the PFS and OS (p < 0001). Sex (male vs. female, HR, 1.831; 95% CI, 1.016-3.303), clinical stage (HR, 1.282; 95% CI, 1.069-1.537), accumulative radiation dose (≥41.4 Gy vs. <41.4 Gy; HR, 0.640; 95% CI, 0.413-0.993), salvage surgery (yes vs. no, HR: 0.412, 95% CI: 0.298-0.570), and regimen (PF vs. PC; HR, 1.514; 95% CI, 1.109-2.067) were independent prognostic factors for cancer mortality. CONCLUSION: Compared with the PF regimen, the PC regimen for definitive CRT yielded significantly increased response rates and longer survival times; therefore, the PC regimen may be preferable for chemotherapy for definitive CRT in patients with advanced ESCC.

Discrepancy of Breast and Axillary Pathologic Complete Response and Outcomes in Different Subtypes of Node-positive Breast Cancer after Neoadjuvant Chemotherapy.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes.

Long-Term Outcomes of Breast Cancer Patients Who Underwent Selective Neck Dissection for Metachronous Isolated Supraclavicular Nodal Metastasis.

We retrospectively enrolled 139 patients who developed metachronous isolated supraclavicular lymph node metastasis (miSLNM) from 8129 consecutive patients who underwent primary surgery between 1990 and 2008 at a single medical center. The median age was 47 years. The median follow-up time from date of primary tumor surgery was 73.1 months, and the median time to the date of neck relapse was 43.9 months in this study. Sixty-one (43.9%) patients underwent selective neck dissection (SND). The 5-year distant metastasis-free survival (DMFS), post-recurrence survival, and overall survival (OS) rates in the SND group were 31.1%, 40.3%, and 68.9%, respectively, whereas those of the no-SND group were 9.7%, 32.9%, and 57.7%, respectively (p = 0.001). No SND and time interval from primary tumor surgery to neck relapse ≤24 months were the only significant risk factors in the multivariate analysis of DMFS (hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.56; p = 0.002 and HR, 1.76, 95% CI, 1.23-2.52; p = 0.002, respectively) and OS (HR, 1.77; 95% CI, 1.22-2.55; p = 0.003 and HR, 3.54, 95% CI, 2.44-5.16; p < 0.0001, respectively). Multimodal therapy, including neck dissection, significantly improved the DMFS and OS of miSLNM. Survival improvement after miSLNM control by intensive surgical treatment suggests that miSLNM is not distant metastasis.

Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study.

PURPOSE: This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC). METHODS: At 40 sites in Taiwan, USA, Korea, India, and Hong Kong, patients with MBC of any molecular subtype and ≤2 prior progressive disease events with stable/responding disease after the last anticancer regimen were randomized (2:1) to adagloxad simolenin (AS/OBI-821) or placebo, subcutaneously for nine doses with low-dose cyclophosphamide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, correlation of clinical outcome with humoral immune response and Globo H expression, and safety. RESULTS: Of 349 patients randomized, 348 received study drug. Patients with the following breast cancer subtypes were included: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (70.4%), triple negative (12.9%), and HER2+ (16.7%), similarly distributed between treatment arms. Median PFS was 7.6 months (95% CI: 6.5-10.9) with AS/OBI-821 (n=224) and 9.2 months (95% CI: 7.3-11.3) with placebo (n=124) (HR=0.96; 95% CI: 0.74-1.25; p=0.77), with no difference by breast cancer subtype. AS/OBI-821 recipients with anti-Globo H IgG titer ≥1:160 had significantly longer median PFS (11.1 months (95% CI: 9.3-17.6)) versus those with titers <1:160 (5.5 months (95% CI: 3.7-5.6); HR=0.52; p<0.0001) and placebo recipients (HR=0.71; p=0.03). Anti-KLH immune responses were similar at week 40 between AS/OBI-821 recipients with anti-Globo IgG titer ≥1:160 and those with anti-Globo IgG titer <1:160. The most common adverse events with AS/OBI-821 were grade 1 or 2 injection site reactions (56.7%; placebo, 8.9%) and fever (20.1%; placebo, 6.5%). CONCLUSION: AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307.

Changes in hot flash experiences and related factors in women with breast cancer.

OBJECTIVE: Taiwanese women are younger than women in western countries when diagnosed with breast cancer, and many of them are still menstruating. One of many distressing side effects reported by premenopausal women treated for breast cancer are hot flashes (HFs). The purposes of this study were to identify: (1) the trajectories of hot flash (HF) occurrence, frequency, and interference and (2) potential factors associated with HF changes. METHODS: Peri- or premenopausal women newly diagnosed with breast cancer scheduled to receive chemotherapy and hormonal therapy were enrolled. HF frequency, HF interference, and other symptoms were measured six times from prechemotherapy to 24 months after chemotherapy. Data were analyzed using hierarchical linear modeling. RESULTS: A total of 90 women were eligible for the study. The prechemotherapy occurrence rate of HFs was 7.9%, but rapidly increased to 42.5% immediately after chemotherapy. The change curve of HF frequency and interference appeared quadratic, increasing first and slightly decreasing later. At any time point, increased body mass index (BMI) was associated with both higher HF frequency (P = 0.020) and HF interference (P = 0.002), whereas anxiety (P < 0.001) and loss of sexual desire (P = 0.038) were associated with higher HF interference. Six months after completing chemotherapy, premenopausal women reported significantly higher HF frequency than perimenopausal women (P = 0.041). CONCLUSION: A significant proportion of pre- and perimenopausal women experienced HFs after receiving breast cancer treatment. Our findings on HF trajectories can educate patients newly diagnosed with breast cancer. Special attention should be paid to those with increased body mass index changes and those still regularly menstruating.

Impact of age on pathological complete response and locoregional recurrence in locally advanced breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard approach for downstaging of locally advanced breast cancer and can improve breast conservation rates. A pathological complete response (pCR) after NAC associated with favorable long-term outcomes has been described. There is still a high locoregional recurrence (LRR) rate after NAC and the influence of age on LRR after NAC is unclear. This study analyzed the relationship between age and LRR after NAC. METHODS: Two hundred and sixty-three patients with invasive breast cancer who received NAC followed by mastectomy or breast conserving surgery (BCS) were enrolled. Concurrent weekly epirubicin and docetaxel was the NAC regimen. RESULTS: Twenty-nine patients (11%) achieved a pCR after NAC. In univariate analysis, age <50 years, luminal B (HER2 positive) subtype, HER2 overexpression subtype, and triple-negative subtype were factors to predict a pCR. In multivariate analysis, age <50 years, luminal B (HER2 positive) type, HER2 overexpression, and triple-negative subtype were the independent factors to predict a pCR. No patients in the pCR group developed LRR compared with 31 patients in the non-pCR group. Eleven patients (6.9%) in the younger group (age <50 years) developed LRR compared with 20 patients (19.4%) in the older group (age ≥50 years). In multivariate analysis, younger age (<50 years) was the only independent prognostic factor for a LRR-free survival. CONCLUSION: Younger age can predict a pCR and is an independent prognostic factor for LRR in locally advanced breast cancer patients after NAC as concurrent epirubicin and docetaxel.

Timing and risk of mood disorders requiring psychotropics in long-term survivors of adult cancers: A nationwide cohort study.

BACKGROUND: The increasing number of long-term cancer survivors over the past few decades poses the challenge of mental health care needs. However, little is known about risks of mood disorders in long-term cancer survivors. METHODS: Long-term survivors (≥5 years) of adult cancers (LSAC) (n = 190,748) newly diagnosed between January 1, 2000 and December 31, 2007 were matched with one control. The primary outcome was diagnosis of mood disorders requiring psychotropics. Cumulative incidences and sub-hazard ratios (SHR) were calculated and multivariate analyses were conducted after accounting for mortality. RESULTS: The mood disorder risk was significantly higher in the LSAC cohort than in the control cohort (adjusted SHR = 1.16, 95% confidence interval [CI] = 1.13-1.18, P < 0.001). Patients with certain cancer types were at increased risk, particularly in the first 2 years after diagnosis. However, patients with head and neck cancers or esophageal cancers had a higher risk after the 5-year follow-up period. Multivariate analysis indicated that being female, aged 40-59 years, with more than two primary cancers, receiving two or more treatment modalities, having CCI scores higher than 3, a higher urbanization level, and lower monthly income were independently associated with an increased risk of mood disorders. LIMITATIONS: Some potential confounders such as lifestyle factors were not available in the study. CONCLUSION: These findings call for increased mental health awareness not only in the early years after the cancer diagnosis, but also during long-term follow-up for certain cancer subtypes.

Pretreatment clinical stage predicts locoregional recurrence in patients with esophageal cancer who achieved a complete clinical response to chemoradiotherapy.

OBJECTIVE: Definitive chemoradiotherapy (dCRT) represents a curative nonsurgical treatment option for patients with esophageal cancer. However, tumor recurrence is common after dCRT, even when clinical complete response (cCR) is achieved. Here, we investigated the timing, patterns, and risk factors for recurrence in patients with esophageal squamous cell carcinoma (ESCC) who achieved cCR following dCRT. METHODS: We retrospectively examined the clinical records of patients with ESCC who achieved cCR following dCRT between 2001 and 2014. Locoregional recurrence (LR) was defined as a recurrence occurring in the esophageal lumen and/or locoregional lymph nodes. Recurrences at any other sites were considered as distant recurrences (DRs). RESULTS: A total of 102 patients who achieved cCR were included. After a mean follow-up of 54.5 months, 51 patients developed recurrences (34 LRs, 6 combined LR and DR, and 11 DRs). The cumulative 1-, 3-, and 5-year recurrence rates were 35%, 46%, and 50%, respectively. The mean time to recurrence for the 40 patients with LRs (including LRs plus LRs/DRs) was significantly shorter (281.4 days) compared with that of patients with DRs (643.6 days; P = .006), with 95% of the former being diagnosed within 2 years. Multivariate Cox regression analysis identified pretreatment clinical stage III as the only independent risk factor for LR (hazard ratio, 2.732; 95% confidence interval; 1.063-7.020; P = .037). CONCLUSIONS: Disease recurrence occurs in 50% of ESCC patients who achieve cCR following dCRT, with LR being the most common pattern. Advanced pretreatment clinical stage is an independent risk factor for LR.

Anatomical distribution of residual cancer in patients with oesophageal squamous cell carcinoma who achieved clinically complete response after neoadjuvant chemoradiotherapy.

OBJECTIVES: Recent advances in neoadjuvant chemoradiotherapy (nCRT) have significantly increased the rates of pathological complete response achieved by patients with oesophageal cancer. Consequently, a watchful waiting strategy based on 'active endoscopic surveillance and surgery as needed' has been proposed for cases without clinical evidence of disease after neoadjuvant chemoradiotherapy. Here, we investigated whether endoscopic surveillance is a reliable tool for the detection of the initially unidentified residual cancer in this patient group. METHODS: We performed a careful pathological re-review of all cases with oesophageal squamous cell carcinoma, who attained a clinical complete response, despite showing a pathological non-complete response. The detailed anatomical locations of such unidentified malignancies were investigated in each patient to determine the prevalence of cancer involvement for each oesophageal layer. RESULTS: Among the 73 patients with clinical complete response, 46 (63%) patients were found to have pathological non-complete response. The majority (89.1%; n = 41) of patients had evidence of residual cancer in the oesophagus, whereas only 5 (10.9%) patients had T0N+ disease. However, a high percentage (39.1%; n = 16) of patients had no detectable cancer in the mucosa and 9 of them also had no detectable cancer in sub-mucosal layer, ultimately hampering their detection via endoscopic biopsy. CONCLUSIONS: Nearly 40% of patients with oesophageal squamous cell carcinoma who attained clinical complete response but showed a pathological non-complete response had residual cancer hidden underneath a cancer-free mucosa layer.

An analysis of factors affecting the accuracy of endoscopic biopsy after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

PURPOSE: The accuracy of endoscopic esophageal biopsy after neoadjuvant chemoradiotherapy (nCRT) remains suboptimal. We retrospectively examined the factors that may affect the diagnostic accuracy of post-nCRT endoscopic biopsy in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A total of 213 ESCC patients were enrolled. Biopsy findings were cross-checked against the final pathology outcomes (ypT0 versus non-ypT0) to assess their accuracy. The independent predictors of diagnostic accuracy were identified by multivariate logistic regression analysis. RESULTS: Post-nCRT endoscopic biopsy results were diagnostically consistent with the final pathology outcomes in 116 (54.5%) patients. Multivariate logistic regression analysis identified a long time interval between the completion of nCRT and the endoscopic examination as the only factor independently associated with a higher diagnostic accuracy. Receiver operating characteristic curve analysis showed that the optimal cutoff value for the time interval between nCRT completion and endoscopic biopsy was 45 days. The estimated diagnostic accuracies of biopsies performed before and after the optimal cutoff time were 49.1% and 72.9%, respectively. CONCLUSIONS: Endoscopic biopsies performed ≥45 days after nCRT are associated with a higher diagnostic accuracy. This time cutoff may serve as a reference to inform the choice of the optimal treatment strategy following nCRT, especially among complete responders in whom surgery withholding is being considered.

Impact of Detection Method and Accompanying Ductal Carcinoma in Situ on Prognosis of T1a,bN0 Breast Cancer.

Background: T1a,bN0 breast cancer is not easily detected. Before mammography became widespread, most cases were discovered only after the development of symptoms. The presence of ductal carcinoma in situ (DCIS) affects the detectability of associated invasive cancer; however, the prognostic value of concomitant DCIS is controversial. This study compared the characteristics of screening-detected and symptom-detected T1a,bN0 breast cancer, and investigated the impact of accompanying DCIS on detection and prognosis. Patients and Methods: Data were collected from a single hospital between 2000 and 2009. Of 5,690 primary breast cancers patients, 438 met the criteria for T1a,bN0M0. Logistic regression models were used to identify prognostic indicators and their association with the detection method. Survival analyses were performed to estimate distant relapse-free survival (DRFS) and breast cancer-specific survival (BCSS). Results: Tumors in 79 and 359 patients were detected by screening and development of symptoms, respectively. Symptomatic cancer patients were younger, more likely to receive a mastectomy, and had larger accompanying DCIS lesions; their 10-year DRFS rates were worse than those of patients with screening-detected tumors (91.1% vs. 100% respectively, p=0.049). Patients with large accompanying DCIS (≥2 cm) had markedly worse 10-year DRFS (77.1% vs. 97.4%, p<0.001) and BCSS (94.3% vs. 98.9%, p<0.001). Conclusion: T1a,bN0 breast cancers detected owing to symptoms are more likely to have larger accompanying DCIS. T1a,bN0 patients with large accompanying DCIS have worse DRFS and BCSS. It is important to consider associated DCIS size when evaluating prognosis in T1a,bN0 breast cancer patients.

GALNT14 genotype as a response predictor for concurrent chemoradiotherapy in advanced esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is an aggressive cancer. We investigated genetic response predictors for patients with advanced esophageal squamous cell carcinoma receiving concurrent chemoradiotherapy. A cohort of 108 patients was recruited. Survival analysis showed that lower esophageal location of tumor, more advanced metastasis stage, and longer length of tumor were associated with poorer overall survival (adjusted P = 0.001, < 0.001, and 0.045, respectively), while the presence of complete/partial response to concurrent chemoradiotherapy was independently associated with better overall survival (adjusted P < 0.001). The GALNT14-rs9679162 "GG" genotype was associated with a lower rate of response (P = 0.014). Multivariate Cox-proportional hazards models also showed that the "GG" genotype was associated with a longer time to complete/partial response (adjusted P = 0.022), independent of leukocyte counts and gender. In conclusion, the presence of a complete/partial response to chemoradiotherapy was critical for advanced esophageal squamous cell carcinoma patients to achieve better overall survival. The GALNT14-rs9679162 "GG" genotype was associated with a longer time to complete/partial response of concurrent chemoradiotherapy.

Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance.

BACKGROUND: Esophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor-free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT. METHODS: Between 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures. RESULTS: Sixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively. CONCLUSIONS: PPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.

Development of a nomogram for the prediction of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Nomograms incorporating multiple prognostic factors are useful for individualized estimation of survival in cancer patients. However, nomograms for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer are scarce. Here, we describe the development of a nomogram for predicting pCR after nCRT in patients with esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the records of 392 ESCC patients who underwent nCRT followed by esophagectomy. Seventy percent of the participants (n = 274) were randomly assigned to a training cohort, whereas the remaining 30% were included in a validation cohort (n = 118). Data from the training cohort were subjected to multivariate logistic regression analyses for selecting variables to be included in the nomogram. The performance of the resulting nomogram was internally and externally validated by calculating the bias-corrected concordance statistic (c-statistic) and the area under the receiver operating characteristics curve (AUROC) in the training and validation cohorts, respectively. After surgery, 25.77% of the study patients achieved pCR. The following variables were included in the nomogram: (i) age, (ii) pretreatment tumor length, (iii) history of head and neck cancer, (iv) post-nCRT albumin levels, and (v) post-nCRT endoscopic findings coupled with endoscopic biopsy results. The bias-corrected c-statistic and AUROC of the internal and external validation sets were 0.77 and 0.747, respectively. Our nomogram showed a good performance for predicting pCR after nCRT in ESCC patients.

Survival outcomes of consolidation chemoradiotherapy in esophageal cancer patients who achieve clinical complete response but refuse surgery after neoadjuvant chemoradiotherapy.

Some esophageal cancer patients may be reluctant to accept the scheduled resection after neoadjuvant chemoradiotherapy (nCRT) because of its potential negative impact on quality of life as a result of high morbidity. This study was performed to investigate the survival outcomes of these patients. Between 2000 and 2012, we identified 190 patients with resectable esophageal squamous cell carcinoma (ESCC) who did not proceed to surgery following nCRT. Subjects who had a clinical complete response (cCR) and were medically fit for surgery were deemed eligible. Survival rates, recurrence patterns, and risk factors for recurrence served as the main outcome measures. The study cohort consisted of 73 patients (67 males and 6 females; mean age: 61.3 years). The 5-year overall survival was 39.6% (median survival time: 46.77 months). Cancer recurrences were observed in 44 patients (60.2%), with locoregional recurrence (LR) being the most common failure pattern (n = 35). Endoscopic findings after nCRT were the most important independent predictor of LR identified in multivariate analysis. Compared with the 'normal findings' subgroup, the odds ratios for LR in cCR patients who refused surgery were 4.774 (P = 0.026) and 2.844 (P = 0.16) in the 'scar' and 'other findings' subgroups, respectively. Patients with 'normal findings' had the lowest rate of LR (22.2%), with no recurrences occurring within the first 6 months. Sixty percent of ESCC patients who achieve cCR following nCRT but refuse esophagectomy develop disease recurrence, with LR being the most common pattern. Post-nCRT endoscopic findings may serve as a predictor for LR.

Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted.

Postoperative Adjuvant Therapy Improves Survival in Pathologic Nonresponders After Neoadjuvant Chemoradiation for Esophageal Squamous Cell Carcinoma: A Propensity-Matched Analysis.

BACKGROUND: The prognosis of patients with esophageal cancer who have poor response to chemoradiotherapy (ie, pathologic nonresponders [pNRs]) remains poor. We investigated whether the use of postoperative adjuvant therapy (AT) could improve survival in this patient group. METHODS: Among patients with esophageal squamous cell carcinoma who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation between 2000 and 2012, pNRs (defined as those having a postoperative T stage of equal or greater pretreatment T stage or persistent nodal disease) were identified and divided into two groups according to their subsequent management (AT versus surveillance). Survival and recurrence were compared after propensity score matching for the following five factors: age, performance status, pathological lymph node status after treatment (ypN) status, severity of postoperative complications, and length of hospital stay (LOS). RESULTS: Of the 115 pNRs, 74 and 41 received AT and surveillance alone, respectively. Patients who received AT were younger, had less major postoperative complications, and a shorter LOS. A total of 32 pairs of well-balanced patients (n = 64) were selected by propensity matching. A significant benefit in terms of disease-free survival (DFS) was observed for pNRs treated with AT compared with those undergoing surveillance (3-year DFS rate: 45% versus 22.3%, p = 0.022). However, more patients in the AT group died of causes unrelated to cancer, resulting only in a borderline increase of overall survival (OS) [3-year OS rate: 34.4% versus 21.6%, p = 0.13]. CONCLUSIONS: Postoperative AT can improve DFS in pNRs after nCRT. However, its use should be carefully weighed against a potential increase in the risk of treatment-related death.

Expression of ROR1 has prognostic significance in triple negative breast cancer.

Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4 %) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; P = 0.00015), distant metastasis-free survival (DMFS; P = 0.00013) and overall survival (OS; P = 0.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3 %) with medullary features showed longer OS (P = 0.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness.

Identification of patients with hormone receptor-positive breast cancer who need adjuvant tamoxifen therapy for more than 5 years.

BACKGROUND/PURPOSE: Extended hormonal therapy with tamoxifen for > 5 years has improved disease-free survival (DFS) and overall survival (OS) in hormone receptor (HR)-positive breast cancer patients. The aim of this study was to identify the HR-positive breast cancer women who need adjuvant tamoxifen for > 5 years. METHODS: Between 1990 and 2004, 1104 HR-positive breast cancer patients who had received tamoxifen treatment at our institution and had been disease free for at least 6 years were included in this analysis. Univariate and multivariate analyses of prognostic factors for late recurrence were performed using the binary logistic regression model. RESULTS: During a median follow-up period of 10.9 years after surgery, 70 patients died and 99 showed recurrence. In multivariate analysis, age < 40 years (p < 0.001) and lymph node metastasis (p < 0.001) were associated with higher rates of recurrence. We stratified patients into high-risk (age < 40 years or positive lymph node status, 536 patients) and low-risk (age > 40 years and negative lymph node status, 566 patients) groups. The recurrence rates were 14.6% and 3.5% in the high-risk and low-risk groups, respectively. Patients in the high-risk group had poorer disease-free survival (p < 0.001) and overall survival (p = 0.010) than those in the low-risk group. CONCLUSION: Our findings suggest that HR-positive breast cancer women either aged < 40 years or with positive lymph node status were justified in continuing with tamoxifen therapy for > 5 years.

High sex determining region Y-box 2 (SOX2) expression correlates with absence of nodal metastasis in esophageal squamous cell carcinoma.

Sex determining region Y-box 2 (SOX2) is a transcription factor involved in self-renewal and pluripotency. Dysregulation of SOX2 expression has been found in squamous cell carcinoma (SCC), including esophageal SCC. Recently, high SOX2 expression was found to be a negative predictor of occult lymph node metastasis in early oral SCC, but the clinical significance of SOX2 expression in esophageal SCC remains controversial. Here we investigated SOX2 expression by immunohistochemistry in 75 cases of surgically resected esophageal SCC. Similar to oral SCC, we found for the first time that high SOX2 expression correlates with absence of clinical nodal metastasis (P = 0.011). Podoplanin is a glycoprotein which is variably expressed by esophageal SCC. Since we previously found that podoplanin expression correlates with nodal metastasis in esophageal SCC, we also assessed podoplanin expression in these cases. Interestingly, SOX2 expression correlates negatively with podoplanin expression (P = 0.018). It is in contrast with a recent finding that SOX2 can up-regulate podoplanin expression in SCC of the skin. Our result suggests that SOX2 might suppress nodal metastasis through down-regulation of podoplanin in esophageal SCC. Further studies are needed to clarify the exact mechanism of regulation.