Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients

Purpose

The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy.

Methods

One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones.

Results

For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9?months, p?=?0.116; 7.0 vs. 7.8?months, p?=?0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9?months, p?=?0.014; 9.1 vs. 7.9?months, p?=?0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p?=?0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p?=?0.005).

Conclusions

ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.     

Phase II study of S-1 monotherapy in patients with previously treated, advanced non-small-cell lung cancer

Background

In this phase II clinical trial, we evaluated the efficacy and safety of S-1 monotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We also measured plasma concentrations of 5-fluorouracil (5-FU) and 5-chloro-2,4-dihydroxypyridine components of S-1 and examined correlation with effectiveness and toxicity.

Methods

S-1 was given orally at a dose of 80?mg/m²/day for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity.

Results

We enrolled 30 patients. The response rate was 26.7% (8/30), and the disease control rate was 70% (21/30). Median progression-free survival (PFS) was 3.1?months, and median overall survival (OS) was 11.2?months. Mutations in the epidermal growth factor receptor (EGFR) gene were analyzed in 27 patients. The response rate was higher in patients with mutant EGFR (50.0%) than in those with wild-type EGFR (11.8%, P?=?0.0288). Median PFS was 4.8 and 2.5?months (P?=?0.038), and median OS was 22.4 and 8.4?months (P?=?0.071). There was no grade 4 toxicity in this study. Five patients had grade 3 non-hematologic toxicity, and there was a trend toward higher plasma concentrations of 5-FU in those patients than in another patients.

Conclusions

S-1 monotherapy is effective and well-tolerated treatment for previously treated advanced NSCLC.     

Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis

Background

It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.

Methods

We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.

Results

In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1?months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4?months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8?months, and the median overall survival (OS) was 12.2?months. Compared with patients with an RFI of <6?months (n?=?25), patients with an RFI of ≥6?months (n?=?27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2?months, respectively), and longer overall survival (7.3 vs. 16.6?months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6?months was still significantly associated with PFS and OS.

Conclusions

S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6?months.     

Prognostic significance of breast cancer subtype and p53 overexpression in patients with locally advanced or high-risk breast cancer treated using upfront modified radical mastectomy with or without post-mastectomy radiation therapy

Background

Although post-mastectomy radiation therapy (PMRT) has shown benefits, its effects in patient subpopulations remain uncertain. Therefore, we assessed whether breast cancer subtype and p53 overexpression were associated with outcome after modified radical mastectomy (MRM), with or without PMRT.

Methods

We retrospectively analyzed the records of patients who underwent MRM, with or without PMRT, between January 1991 and December 2008. Patients were considered eligible if they had T3 or T4 stage disease; any T stage with N2 or N3 stage; any T or N stage with positive, close (<1?mm) resection margins; or skin, nipple, or pectoral muscle invasion. We used immunohistochemistry and/or fluorescent in situ hybridization to determine breast cancer subtypes and p53 overexpression status.

Results

We found that 104 patients were eligible, including 59 (56.7%) who underwent PMRT and 45 (43.3%) who did not. Median follow-up duration was 61.3?months (range 16.1–232.7). Overall survival (OS) was significantly longer in patients who underwent PMRT (P?=?0.029). This trend was evident in the subgroup of luminal type A breast cancer (P?=?0.017) and non-p53 overexpression (P?=?0.026) patients. However, there was no significant survival benefit from PMRT in the subgroup of triple negative (TN) breast cancer (P?=?0.528) and p53 overexpression (P?=?0.189) patients.

Conclusions

The benefit of PMRT differed among subgroups with different breast cancer subtype and p53 overexpression. More efficacious systemic treatment strategies are needed, especially in patients at high risk for distant metastasis, to obtain optimal therapeutic gain.     

Pulmonary metastasectomy in patients with renal cell carcinoma: a single-institution experience

Background

Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution.

Methods

We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution.

Results

All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P?=?0.004, 0.012, respectively).

Conclusions

The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.     

Three-week combination chemotherapy with S-1 and cisplatin as first-line treatment in patients with advanced gastric cancer: a retrospective study with 159 patients

Background

Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes.

Methods

A total of 159 patients with AGC were treated with S-1 (40?mg/m² bid on days?1–14) and cisplatin (60?mg/m² IV on day?1) between January 2004 and December 2008.

Results

Median follow-up duration was 20.0?months (range, 11.4–48.5?months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1–19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0–61.8%). The median progression-free survival (PFS) was 5.8?months (95% CI, 4.8–6.9?months), and the median overall survival (OS) was 11.3?months (95% CI, 9.6–13.0?months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P?Conclusions A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors.     

Fifty percent patients avoid whole brain radiotherapy: stereotactic radiotherapy for multiple brain metastases. A retrospective analysis of a single center

Purpose

To summarize the outcomes of stereotactic radiotherapy (SRT), with or without whole-brain radiotherapy (WBRT), in the treatment of multiple brain metastasis and to explore the status of WBRT and SRT in the management of multiple brain metastasis.

Methods

From May 1995 to April 2010, 98 patients with newly diagnosed, multiple brain metastasis were treated in our center. Forty-four patients were treated with SRT alone for the initial treatment, and 54 were treated with SRT?+?WBRT. Kaplan?CMeier and Cox proportional hazards regression analyses were used for the survival analysis.

Results

The median survival time (MST) was 13.5?months. No difference was observed in MST between the SRT and the SRT?+?WBRT groups (p?=?0.578). The Karnofsky Performance Score at the time of treatment (p?=?0.025), the interval time between diagnosis of primary tumor and brain metastasis (P?=?0.012) and the situation of extracranial disease (p?=?0.018) were significant predictors of survival. The crude distant intracranial recurrence (DIR) rates were 47.7?% in the SRT group and 24.1?% in the SRT?+?WBRT group (p?=?0.018). In addition, 52.3?% patients in the SRT group were free from DIR and did not require WBRT in their whole lives.

Conclusions

Our data suggest that use of SRT as the initial treatment while reserving WBRT as the salvage therapy in case of distant intracranial recurrence made about 50?% of the patients avoid WBRT throughout the course of their lives and may be another optional treatment modality for multiple brain metastases.     

Second-line chemotherapy for advanced or recurrent endometrial carcinoma previously treated with paclitaxel and carboplatin, with or without epirubicin

Purpose

A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline.

Methods

During the 2000?C2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed.

Results

Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of ???or?<6?months was demonstrated to be significantly associated with the response to second-line chemotherapy (P?=?0.0026), progression-free survival (P?=?0.0003) and overall survival (P?=?0.025). The second-line chemotherapy similar to the first-line regimen was ineffective in all the 7 cases (100%) whose TFI was shorter than 6?months. Multivariate analysis showed that TFI was the most significantly important factor predicting the effectiveness of second-line chemotherapy (the adjusted hazard ratio of TFI on PFS and OS: 3.482, 95% CI, 1.641?C7.388, P?=?0.0012, and 2.341, 95% CI, 1.034?C5.301, P?=?0.042, respectively).

Conclusions

Our present study provides, for the first time, evidence that the majority of refractory or recurrent diseases, if they occur within 6?months of a first-line chemotherapy using taxane and platinum with or without anthracycline, are non-responsive to the current regimens of second-line chemotherapy.     

Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study

Objective

To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy.

Methods

In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4?months for a mean follow-up period of 39.0?months, with cytologic regression defined as two consecutive negative smears and normal colposcopy.

Results

In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2?years; the difference in the 2-year risk of CIN3+?between the two groups was marginally significant (0 vs. 5.5%; P?=?0.07). The cumulative probability of cytologic regression within 12?months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P?=?0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P?=?0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P?=?0.73).

Conclusion

In women with biopsy-negative LSILs, the risk of CIN3+?diagnosed within 2?years was low; furthermore, approximately 70% underwent cytologic regression within 12?months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.     

Prognosis Impact of the Lymph Node Ratio in Patients with Colon Adenocarcinoma: a Single-Centre Experience

Purpose

Recently, the positive lymph node ratio (LNR) is considered a new prognostic parameter on survival and time to progression for patients with colon cancer. The aim of this study was to determine the prognostic impact of the LNR as an independent factor for overall survival (OS) and disease-free survival (DFS) in patients with colon cancer regardless of their clinical stage.

Methods

We retrospectively identified 85 consecutive patients diagnosed with colon adenocarcinoma treated in our centre during 2010. We categorized patients according to a LNR cutoff of 0.25. Three-year OS and DFS were determined according to the Kaplan–Meier method. A Cox proportional model was used to assess the influence of other prognostic variables on each outcome.

Results

After median follow-up of 34.8 months, neither median OS nor DFS has been reached by any of the subgroups. Nevertheless, patients with a LNR?≥?0.25 exhibited a higher risk of death (hazard ratio, 3.10; 95 % confidence interval (CI), 1.38–7.01; log-rank test: p?=?0.006) and a shorter interval without progression (hazard ratio, 6.59; 95 % CI, 1.96–22.15; log-rank test: p?=?0.002.) than patients with LNR?<?0.25. After adjusting for prespecifed variables, the impact of a LNR?≥?0.25 was independently associated with OS (hazard ratio, 2.8; 95 % CI, 1.01–7.73; p?=?0.04) and DFS (hazard ratio, 7.07; 95 % CI, 1.23–40.45; p?=?0.03).

Conclusions

LNR was independently associated with OS and DFS in patients with colon adenocarcinoma regardless of its clinical stage.     

Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer

Background

Neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, has been associated with worse survival for many types of cancer. The aim of this study is to investigate the clinical significance of the blood NLR as a prognostic factor in non-small cell lung cancer (NSCLC) patients.

Methods and patients

Stage IV NSCLC patients diagnosed in our institution between April 2004 and March 2009 were retrospectively reviewed. Potential prognostic factors such as histology, gender, performance status, response to chemotherapy and NLR were analyzed. NLR was assessed baseline and during chemotherapy treatment. Overall survival (OS) and progression free survival (PFS) were calculated by the Kaplan?CMeier method.

Results

A total of 171 patients were included in the study and 60 patients (35.1?%) presented a NLR ??5. Median survival for the entire cohort was 9.3?months. We found that patients with undifferentiated carcinoma and patients with NLR ??5 had a worse survival. Median PFS of patients with NLR <5 was 5.62?months and in patients with NLR ??5 was 3.25?months (p?=?0.098), and OS was 11.1 versus 5.6?months for patients with NLR<5 and NLR ??5, respectively (p?=?0.017). During the chemotherapy treatment, patients who normalized NLR after one cycle presented better outcomes (OS 8.7 vs. 4.3?months, p?=?0.001, for patients who normalized NLR and for patients who remained persistently elevated). After multivariate analysis, histology and NLR remained independent predictors of survival (p?<?0.05).

Conclusion

In our analysis, elevated NLR is a predictor of shorter survival in patients with advanced NSCLC and the variation of NLR during the first cycle of treatment predicts survival. NLR is an easily measured, reproducible test that could be considered to be incorporated in the routine practice in NSCLC patients.     

Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia

Purpose

The impact of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) on the efficacy of nilotinib was evaluated.

Methods

Retrospective analyses were performed in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP; N?=?492) and in patients with imatinib-resistant or imatinib-intolerant Ph+ CML-CP (N?=?256) treated with nilotinib.

Results

In the newly diagnosed population, 87 (17.7?%) and 49 (10.0?%) patients received PPIs and H2 blockers, respectively. Major molecular response at 12?months was achieved by 59 (49.6?%) patients who received at least one PPI or H2 blocker (n?=?119) and 153 (41.0?%) patients who did not receive any comedication (n?=?373; P?=?0.13). PPIs and H2 blockers were used by 77 (30.1?%) and 17 (6.6?%) patients with imatinib-resistant or imatinib-intolerant CML-CP, respectively. Major cytogenetic response by 12?months was achieved by 55 (64.0?%) patients who received at least one PPI or H2 blocker (n?=?86) versus 98 (57.6?%) patients who did not receive any comedication (n?=?170; P?=?0.40); 39 (45.3?%) versus 65 (38.2?%), respectively, achieved complete cytogenetic response by 12?months (P?=?0.34). Similar findings were observed in patients who received comedication for >50?% of the time on nilotinib therapy. Nilotinib steady-state trough concentration was not affected by the presence of PPIs or H2 blockers.

Conclusions

Concurrent use of PPIs or H2 blockers did not affect the pharmacokinetics and efficacy of nilotinib in patients with Ph+ CML-CP.     

Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer: a retrospective study with pharmacogenetic evaluation

Purpose

In the present study, the combination of carboplatin (CBDCA) plus pemetrexed (PMX) for the treatment of patients with platinum-pretreated, pemetrexed-na?ve, advanced non-small cell lung cancer (NSCLC) was investigated. Also, single nucleotide polymorphisms (SNPs) at the XRCC3, XPD, ERCC1, GARFT, DHFR, and TS genes were investigated.

Methods

Eighty patients treated with CBDCA/PMX at two Italian institutions were evaluable. Of these, 73 patients had blood samples collected for pharmacogenetic evaluation.

Results

Overall, the median age was 59?years (26?C78), 59 patients (73.7%) had a performance status of 0, and 34 patients (42.5%) had stage IIIB disease. Thirty-eight patients (47.5%) had responded to prior first-line platinum-based therapy. Study treatment resulted into one complete and 33 partial responses for an overall response rate of 42.5%. The disease control rate was 77.5%. The median progression-free survival (PFS) and overall survival (OS) were 5.8?and 17.4?months, respectively. Responders achieved a significant longer PFS and OS versus non-responders (P?=?0.007 and P?=?0.003, respectively). The only grade 3?C4 adverse event occurring in more than 5.0% of patients was neutropenia (6 patients, 7.5%). No statistically significant association was noted between polymorphisms of the genes analyzed and clinical outcome.

Conclusions

In patients with platinum-pretreated, advanced NSCLC and favorable clinical prognostic factors, treatment with CBDCA/PMX is associated with a good clinical outcome and toxicity profile. None of the SNPs analyzed was found to be a useful predictor of treatment efficacy.     

Colorectal obstruction is a potential prognostic factor for stage II colorectal cancer

Background

Obstructive colorectal cancer (CRC) is an emergency situation with high morbidity and mortality, but long-term outcomes of stage II/III obstructive CRC remain unclear. The aim of this study was to evaluate prognostic factors, including colorectal obstruction.

Methods

Data were retrospectively reviewed from consecutive patients with stage II/III CRC who underwent curative surgery between January 2007 and December 2011 at two Japanese institutions. We analyzed overall survival (OS) and relapse-free survival (RFS), according to various prognostic factors including colorectal obstruction.

Results

In total, 979 patients with stage II/III CRC were identified for this study. Among these 979 patients, 94 patients showed colorectal obstruction (9.6%). In both stage II and stage III CRCs, colorectal obstruction showed significantly poorer OS and RFS compared to non-obstruction (5-year OS, obstruction vs. non-obstruction, stage II: 65.9 vs. 86.5%, P?=?0.002; stage III: 55.9 vs. 73.6%, P?=?0.007) (5-year RFS, obstruction vs. non-obstruction, stage II: 59.2 vs. 77.8%, P?=?0.008; stage III 31.3 vs. 56.3%, P?=?0.001). Multivariate analysis demonstrated colorectal obstruction as a significant independent and poor prognostic factor in terms of both OS (hazard ratio (HR) 2.469; 95% CI 1.339–4.545; P?=?0.004) and RFS (HR 1.992; 95% CI 1.160–3.425; P?=?0.012) for stage II CRC, as well as pT4 stage. On multivariate analysis for stage III CRC, colorectal obstruction was a significant predictor of poor RFS (HR 1.626; 95% CI 1.070–2.469; P?=?0.023), but not poor OS.

Conclusions

Colorectal obstruction is an independent poor prognostic factor for stage II CRC. Adjuvant chemotherapy might be feasible for stage II CRC with colorectal obstruction.

     

Preoperative Platelet Count Associates with Survival and Distant Metastasis in Surgically Resected Colorectal Cancer Patients

Objective

Platelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.

Design

Using a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.

Results

Patients with clinically high platelet count (≥400?×?10⁹/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR]?=?1.66, 95 % confidence interval [CI] 1.34–2.05, P?=?2.6?×?10^?6, P _{log rank}?=?1.1?×?10^?11) and recurrence (HR?=?1.90, 1.24–2.93, P?=?0.003, P _{log rank}?=?0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR?=?2.81, 1.67–4.74, P?=?1.1?×?10^?4, P _{log rank}?=?2.6?×?10^?6) but not locoregional recurrence (HR?=?0.59, 95 % CI 0.21–1.68, P?=?0.325, P _{log rank}?=?0.152). The findings were internally validated through bootstrap resampling (P?<?0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P?<?0.0001) and in patients with metastatic recurrence than locoregional (P?=?0.004) or nonrecurrent patients (P?<?0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.

Conclusion

Our data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.     

Individualized induction chemotherapy by pre-treatment plasma Epstein-Barr viral DNA in advanced nasopharyngeal carcinoma

Background

The role of pretreatment Epstein-Barr virus DNA (pre-DNA) for individualized induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) still remains unknown. We aimed to address this clinical issue.

Methods

In total, data on 6218 patient with newly diagnosed LA-NPC receiving concurrent chemoradiotherapy (CCRT) with or without IC were retrospectively reviewed. Receiver operating characteristics (ROC) curve was adopted to calculate the cut-off value of pre-DNA based on disease-free survival (DFS). Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes between IC?+?CCRT and CCRT groups were compared.

Results

Among the original cohort, no survival difference between IC?+?CCRT and CCRT groups was found. The cut-off value of pre-DNA was 4650 copies/ml (area under curve [AUC], 0.620; sensitivity, 0.6224; specificity, 0.5673). For patients with Pre-DNA?≤?4650 copies/ml, the IC?+?CCRT and CCRT groups also achieved comparable survival outcomes (P?>?0.05 for all rates). However, IC?+?CCRT was associated with significantly improved 3-year DFS (78.6% vs. 74.8%, P?=?0.03), overall survival (OS; 91.4% vs. 87.5%, P?=?0.002) and distant metastasis-free survival (DMFS; 86.0% vs. 82.2%, P?=?0.036) for patient with pre-DNA?>?4650 copies/ml. Multivariate analysis also confirm that IC?+?CCRT was an independent prognostic factor for DFS (HR, 0.817; 95% CI, 0.683–0.977; P?=?0.027), OS (HR, 0.675; 95% CI, 0.537–0.848; P?=?0.001) and DMFS (HR, 0.782; 95% CI, 0.626–0.976; P?=?0.03).

Conclusions

Pre-DNA may be a feasible and powerful consideration for individualized IC apart from other baseline clinical characteristics in LA-NPC.

     

Additional radiation boost to whole brain radiation therapy may improve the survival of patients with brain metastases in small cell lung cancer

Background

The role of the dose escalation strategy in brain radiotherapy for small cell lung cancer (SCLC) patients with brain metastases (BMs) has not been identified. This study aims to determine whether an additional radiation boost to whole brain radiation therapy (WBRT) has beneficial effects on overall survival (OS) compared with WBRT-alone.

Methods

A total of 82 SCLC patients who were found to have BMs treated with WBRT plus a radiation boost (n =?33) or WBRT-alone (n =?49) from January 2008 to December 2015 were retrospectively analyzed. All patients were limited-stage (LS) SCLC at the time of the initial diagnosis, and none of them had extracranial metastases prior to detection of BMs. The primary end point was OS.

Results

The median OS for all of the patients was 9.6?months and the 6-, 12- and 24-months OS rates were 69.1, 42.2 and 12.8%, respectively. At baseline, the proportion of more than 3 BMs was significantly higher in the WBRT group than in the WBRT plus boost group (p?=?0.0001). WBRT plus a radiation boost was significantly associated with improved OS in these patients when compared with WBRT-alone (13.4 vs. 8.5?months; p?=?0.004). Further, the survival benefit still remained significant in WBRT plus boost group among patients with 1 to 3 BMs (13.4 vs. 9.6?months; p?=?0.022).

Conclusion

Compared with WBRT-alone, the use of WBRT plus a radiation boost may prolong survival in SCLC patients with BMs. The dose escalation strategy in brain radiotherapy for selected BMs patients with SCLC should be considered.

     

Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy

Purpose

Prognostic factors for patients with advanced biliary tract cancer receiving chemotherapy are presently not well established. Gallbladder cancer and intra-hepatic cholangiocarcinoma are previously reported prognostic factors of poor prognosis; however, tumor volume has not been analyzed in these previous reports.

Methods

We analyzed 56 consecutive patients with advanced biliary tract cancer who had received gemcitabine and S-1 combination chemotherapy as first-line palliative chemotherapy. Prognostic factors, including the baseline sum longest diameter (BSLD) representing tumor volume in Response Evaluation Criteria in Solid Tumor, were evaluated.

Results

By multivariate analysis, age ??70 (HR 3.01, 95% CI 1.25?C7.31, P?=?0.014) and larger BSLD (HR 1.09, 95% CI 1.01?C1.18, P?=?0.021) were statistically significant independent predictors of poor prognosis. Primary biliary site was not identified as a prognostic factor (P?=?0.728). Median survival times of patients with BSLDs????9.0?cm and BSLDs?>?9.0?cm were 18.7 and 8.8?months, respectively (P?=?0.024).

Conclusions

Age and BSLD were identified as strong prognostic factors for patients with advanced biliary tract cancer receiving chemotherapy. Tumor volume might be more important than primary biliary site for the prognosis of advanced biliary tract cancer.     

Clinical importance of phosphatase of regenerating liver-3 expression in breast cancer

Background

Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors.

Methods

PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by ??2 test. Kaplan?CMeier test and log rank method were used to define prognostic importance of PRL-3 expression.

Results

Of 122 breast cancer tumor samples, 46 (37.7?%) were negative while 76 (62.3?%) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P?=?0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P?=?0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P?>?0.05).

Conclusion

Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group.     

Docetaxel-Based Preoperative Chemoradiation in Localized Gastric Cancer: Impact of Pathological Complete Response on Patient Outcome

Purpose

This study was conducted to evaluate the feasibility, efficacy, and toxicities of docetaxel-based induction chemotherapy and chemoradiotherapy in patients with localized gastric or gastroesophageal adenocarcinoma.

Methods

Patients with localized, operable gastric or gastroesophageal adenocarcinoma received two cycles of induction chemotherapy of fluorouracil, docetaxel, and cisplatin (TPF) followed by 45 Gy of radiation and concurrent fluorouracil plus docetaxel then surgery for nonmetastatic patients.

Results

Forty-one patients were included. Pretreatment T3 was encountered in 56 % of patients while 61 % had N1 disease. A pathologic complete response (CR) was noted in 24 % of patients. Pathologic response was significantly associated with baseline T stage (P?<?0.001) and N stage (P?=?0.002). The 3-year overall survival (OS) and disease-free survival were 47.3 and 42.1 %, respectively. OS was significantly correlated with R0 resection (P?=?0.027), pathological response (P?=?0.01), dissected pathologically positive lymph node (P?=?0.037), and postsurgery (T) stage (P?=?0.02). Toxicities were manageable and there were no treatment-related deaths.

Conclusion

Docetaxel-based chemoradiotherapy in localized gastric adenocarcinoma patients resulted in 24 % path CR and was not associated with a higher percentage of postoperative complications. A well-designed randomized controlled trial is mandatory to further endorse this evolving approach.