KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer

Background

It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC).

Methods

AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc).

Results

KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc.

Conclusion

This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.     

Borderline resectable pancreatic cancer: rationale for multidisciplinary treatment

Background

Borderline resectable pancreatic cancer (BRPC) appears to be most frequently related to a positive surgical margin and has a poor prognosis after resection. However, few reports are available on differences in tumor characteristics and prognoses among resectable pancreatic cancer (PC), BRPC, and unresectable PC.

Methods

Records of 133 patients resected for pancreatic ductal adenocarcinoma and 185 patients treated as locally advanced PC (LAPC) were reviewed.

Results

Twenty-four patients who initially underwent resection (BRPC-s) and 10 patients who were initially treated as LAPC (BRPC-n) met the criteria for BRPC. Prognosis of BRPC was significantly better than that of unresectable PC, but was significantly worse than that of resectable PC. BRPC-s showed more frequent nerve plexus invasion (P < 0.01), portal vein invasion (P < 0.01), and loco-regional recurrence (P = 0.03) than resectable PC. The positive surgical margin rate was not significantly higher in BRPC-s (29%) than in resectable PC (19%) (P = 0.41).

Conclusions

BRPC had a poorer prognosis with more local failure than resectable PC although prognosis of BRPC was significantly better than that of unresectable PC. Considering the tumor and treatment characteristics, multidisciplinary treatment including resection is required for BRPC.     

Definitive chemoradiotherapy with capecitabine and cisplatin for elder patients with locally advanced squamous cell esophageal cancer

Purpose

The aim of this retrospective study is to evaluate the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A total of 75 patients elder than 65 years with histologically proven stage II–III ESCC were enrolled, in whom 40 patients were treated with CCRT consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy and 35 patients were treated with SCRT as two cycles of capecitabine plus cisplatin before and after radiotherapy. Response rate, overall survival, progression-free survival and toxicity were compared.

Results

The overall response rate (CR + PR) in the CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7 %), P = 0.023. The median PFS and median OS were significantly higher in CCRT group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P < 0.05. The acute toxic effect was more severe in the CCRT group than in the SCRT group, but the grade 3–4 acute toxicities were similar in two groups.

Conclusions

It suggested that both CCRT and SCRT with capecitabine and cisplatin are tolerable and effective for elderly patients with locally advanced ESCC. Concurrent CRT might be superior to SCRT.     

CT-guided implantation of radioactive 125I seed in advanced non-small-cell lung cancer after failure of first-line chemotherapy

Purpose

We investigated implanting computed tomography (CT)-guided ¹²⁵I seed to treat locally advanced non-small-cell lung cancer (NSCLC) after chemotherapy failure.

Methods

From January 2005 to July 2010, we recruited 69 patients with locally advanced NSCLC who had each had first-line chemotherapy four to six times but had progressive disease; 34 received ¹²⁵I seed implantation with second-line chemotherapy (Group A) and 35 received second-line chemotherapy only (Group B).

Results

Mean follow-up was 32 months (range 5–56 months). Overall 2-year local control rate for existing lung lesions was Group A: 39.9 %; Group B: 12.5 % (P < 0.05). The 1-, 3-year, and median overall survival was 68.7 and 20.8 % at 17.4 months in Group A; and 45.1 and 18.7 % at 11.3 months in Group B, respectively (P > 0.05). Local 3-, 24-month, and median progression-free survival was Group A: 100 and 79.1 % at 11 months; Group B: 76.5 and 18.7 % at 7.3 months, respectively. The groups did not significantly differ in treatment toxicity. Chest pain remission was Group A: 82.1 % (23/28); Group B: 30.8 % (8/26) (P < 0.05). Group A showed no radiation-related pneumonia, esophagitis, bronchial fistulae, or life-threatening morbidity.

Conclusion

CT-guided radioactive seed ¹²⁵I implantation procedure is safe and well tolerated in treating locally advanced NSCLC, with few complications. It has good local control rate and can relieve symptoms without increasing side effects.     

Neoadjuvant chemotherapy can improve outcome of colorectal cancer patients with unresectable metastasis

Background

The prognosis for colorectal cancer (CRC) patients with unresectable metastases is dismal. This study compared outcomes of different metastatic treatments.

Patients and methods

We collected 653 CRC cases with unresectable metastases including 490 cases receiving primary tumor resection then chemotherapy (surgery group) and 163 patients receiving neoadjuvant chemotherapy then did or did not receive operations (chemotherapy (C/T) group) from 2004 to 2010. The statistical endpoint was overall survival from the date of diagnosis.

Results

In the C/T group, 124 (76 %) patients received an operation after 9.0?±?6.2 months of chemotherapy, including 57 (34.9 %) patients with curative surgery. The C/T group had a higher proportion of T4 lesions (37.4 %) than the surgery group (26.9 %). Survival of the C/T group was longer than that of the surgery group (28.8?±?8.8 vs. 24.3?±?7.5 months; p?=?0.043). Survival of 57 patients receiving curative surgery was 36.0?±?6.3 months, which was significantly better than that of the 67 patients receiving palliative resection (25.2?±?5.6, p?<?0.001). In the surgery group, 42 (8.6 %) patients received curative metastasectomy after 8.5?±?7.1 months of postoperative chemotherapy; survival was 30.8?±?7.8 months, which was significantly better than that of patients who did not receive metastasectomy (22.4?±?6.3 months). In multivariate analysis, poor differentiation, lymphovascular invasion, isolated cancer nodules, clinical risk score, and curative surgery were independent prognostic factors of overall patient survival.

Conclusions

Neoadjuvant chemotherapy can improve outcome of CRC patients with unresectable metastases.     

Clinical implication of additional selective lateral lymph node excision in patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy

Purpose

To identify the indication and prognostic significance of lateral lymph node (LLN) excision in locally advanced rectal cancer patients underwent preoperative chemoradiotherapy.

Methods

Included were 67 consecutive patients with suspicious LLN metastasis who underwent chemoradiotherapy and surgery including selective LLN excision (82 excisions). The excisions were grouped according to the presence of LLN metastasis and compared in terms of the clinicopathological findings and oncological results. The correlation between the largest short-axis diameter of LLN measured by imaging and metastasis rates was explored.

Results

LLN metastases were identified in 32 excisions (40.0 %). The calculated short-axis LLN diameter predicting metastasis was 11.7 mm (before chemoradiotherapy) and 11.4 mm (before surgery). LLN metastasis was observed more frequently in the low rectum (p?=?0.031) and associated with higher CEA levels (p?=?0.048). The 3-year overall survival rates for patients with and without LLN metastasis were 60.3 % and 90.3 % (p?=?0.048), while the 3-year disease-free survival rates were 31.4 % and 70.5 % (p?=?0.009). The hazard ratio of LLN metastasis for recurrence was 2.938 (95 % CI?=?1.258–6.863).

Conclusions

LLN metastasis in rectal cancer patients underwent chemoradiotherapy was a distinct poor prognostic factor. Selective LLN excision based on imaging studies may have a role for such patients.     

Hepatic Arterial Infusion with Oxaliplatin and 5-FU/Folinic Acid for Advanced Biliary Tract Cancer: A Phase II Study

Background

Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer (BTC) has been established recently. However, overall prognosis is still poor, and additional therapeutic approaches are needed for patients with locally advanced, irresectable and/or pretreated tumors. Hepatic arterial infusion (HAI) of chemotherapy represents a safe and well-established treatment modality, but data on its use in patients with BTC are still sparse.

Methods

Patients with irresectable BTC predominant to the liver were included in a prospective, open phase II study investigating HAI provided through interventionally implanted port catheters. Intraarterial chemotherapy consisted of biweekly oxaliplatin (O) 85 mg/m² and folinic acid (F) 170 mg/m² with 5-FU (F) 600 mg/m².

Results

Between 2004 and 2010, 37 patients were enrolled. A total of 432 cycles of HAI were applied with a median of 9 (range 1–46) cycles. Objective response rate was 16 %, and tumor control was achieved in 24 of 37 (65 %) patients. Median progression-free survival was 6.5 months (range 0.5–26.0; 95 % CI 4.3–8.7), median overall survival was 13.5 (range 0.9–50.7; 95 % CI 11.1–15.9) months. The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients.

Conclusions

Using a minimal invasive technique, repetitive HAI with OFF is feasible and results in clinically relevant tumor control with low toxicity in patients with liver predominant advanced BTC.     

High FDG uptake predicts poorer survival in locally advanced nonsmall cell lung cancer patients undergoing curative radiotherapy,independently of tumor size

Objectives

Despite radical radiotherapy and chemotherapy (CT), the prognosis of locally advanced nonsmall cell lung cancer (NSCLC) is poor. New prognostic indicators are being looked forward to improve the survival. [18F]-fluorodeoxyglucose (FDG) uptake on PET/CT has been observed as a prognostic marker mainly in early-stage disease. Our aim was to examine the prognostic value of FDG uptake in locally advanced NSCLC.

Materials and methods

Between 2009 and 2011, 103 NSCLC patients underwent disease staging using FDG PET/CT before conformal radiotherapy. Thoracic radiation was administered at a daily fraction of 2 Gy. Total dose was prescribed according to the tumor response against CT. All patients underwent CT. Survival was estimated using the Kaplan–Meier method.

Results

The median age of the patients was 59 years (range 39–83). The median follow-up time was 22.63 months (range 6–48.03 months). There was a statistically significant difference in overall survival (OS) between the low (<10.7) and high (≥10.7) standardized uptake value (SUVmax) groups (p = 0.006) on univariate analysis (3-year OS was 42 % in the low (<10.7) and 23 % in the high (≥10.7) SUVmax groups). On multivariate analysis with determining tumor size, tumor SUVmax provided additional significant prognostic information on OS (HR 1.046; 95 % CI 1.009–1.085, p = 0.015).

Conclusions

FDG uptake has predictive value in locally advanced NSCLC, independently of tumor size.     

Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy?

Background

According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients.

Methods

We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites.

Results

There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group.

Conclusions

The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.     

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer

Background

The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy.

Methods

The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008.

Results

The proportion with HLN metastasis was 11.5 % in resectable cases and 28.6 % in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P < 0.001), along with non-resection of hepatic lesions (P < 0.001), larger metastatic tumor volume (P < 0.001), non-use of oxaliplatin-based chemotherapy (P < 0.001), involvement of 4 or more regional lymph nodes (P < 0.001), and excessive lymphatic invasion (P = 0.02), was identified as an independent risk factor for shorter survival.

Conclusions

To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.     

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer

Background

The aim of this study was to evaluate the efficacy and morbidity of intraoperative radiation therapy (IORT) for advanced colorectal cancer.

Methods

All patients undergoing IORT for locally advanced rectal cancer from 2001–2009 were reviewed for cancer recurrence, survival, and procedure-related morbidity. Cumulative event rates were estimated using the method of Kaplan and Meier.

Results

Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21) rectal cancers were treated with IORT and resection. Surgical interventions included low anterior resection, abdominoperineal resection, pelvic exenteration, and a variety of non-anatomic resections of pelvic recurrences. R₀ resections were achieved in 16 patients, while R₁ resections were achieved in 10, and margins were grossly positive in 3 patients. IORT was delivered to all patients over a median area of 48 (42–72) cm² at a median dose of 12 (12–15) Gy. Local and overall recurrence rates were 24 % (locally advanced group) and 45 % (recurrent group). Median disease-free and overall survival were 25 and 40 months respectively at a median follow-up of 26 (18–42) months. The short-term (≤30 days) complication rate was 45 %. Eight patients developed local wound complications, 5 of which required operative intervention. Four patients developed intra-abdominal abscesses requiring drainage. Long-term (>30 days) complications were identified in 11 patients (38 %) and included long-term wound complications (n = 3), ureteral obstruction requiring stenting (n = 1), neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n = 1), and neuropathic pain (n = 1).

Conclusions

Intraoperative brachytherapy is a viable IORT option during pelvic surgery for locally advanced or recurrent colorectal cancer but is associated with high postoperative morbidity. Whether intraoperative brachytherapy can improve local recurrence rates for locally advanced or recurrent colorectal cancer will require further prospective investigation.     

Timing of chemotherapy-induced neutropenia is a prognostic factor in patients with metastatic non-small-cell lung cancer: a retrospective analysis in gemcitabine-plus-platinum-treated patients

Purpose

Chemotherapy-induced neutropenia (CIN) has been associated with better therapeutic results in studies of various tumors. Herein, we explored the relationship between timing (onset) of CIN and clinical outcomes of patients with metastatic non-small-cell lung cancer (NSCLC).

Methods

Patients with stage IV NSCLC receiving at least two cycles of first-line doublet chemotherapy (gemcitabine plus platinum) were reviewed retrospectively. Subjects were stratified by onset of CIN into two groups: early-onset (lowest neutrophil count of cycles 1–2 <2.0 × 10⁹/L) and non-early-onset. The non-early-onset group was further subdivided into late-onset (lowest neutrophil count of cycles 3–6 <2.0 × 10⁹/L) and absence of neutropenia.

Results

A total of 123 patients were studied. Significantly better disease control rate, progression-free survival (PFS), and overall survival (OS) were observed in early-onset versus non-early-onset patients. Median PFS of 5.1 and 3.8 months (p = 0.0016) and median OS of 16.7 and 11.2 months (p = 0.0004) were achieved for these groups, respectively. Patient subsets with late-onset and absence of neutropenia showed similarly poor clinical outcomes, with 4.8 and 3.8 months median PFS (p = 0.5067) and 13.0 and 11.2 months median OS (p = 0.6304), respectively.

Conclusions

Timing of CIN is predictive of prognosis in patients with metastatic NSCLC receiving gemcitabine/platinum doublet chemotherapy. Better clinical outcomes were achieved when onset of neutropenia was early versus late or absent altogether. Further research is warranted to determine whether above findings are applicable to other chemotherapeutic regimens.     

Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer

Background

Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration.

Methods

We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data.

Results

From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28–2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58–3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03–3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12–2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44–3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11–2.28) were negative prognostic factors for overall survival.

Conclusions

K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.     

Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy?

Purpose

To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR).

Methods

Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists.

Results

The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8 %). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9 ± 11.9 vs. 68.7 ± 10.8 years, respectively, p = 0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS).

Conclusions

Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.     

Progression-free survival and post-progression survival in patients with advanced gastric cancer treated with first-line chemotherapy

Purpose

The impact of post-progression survival (PPS) on the overall survival (OS) of patients with advanced gastric cancer (AGC) has not yet been reported in detail. We analyzed prospectively collected data from AGC patients who received first-line chemotherapy including fluoropyrimidine plus platinum.

Methods

We partitioned OS into progression-free survival (PFS) and PPS in each patient and analyzed correlations between OS and either PFS or PPS using the Spearman rank correlation coefficient (ρ).

Results

A total of 291 AGC patients met the inclusion criteria with median PFS, PPS, and OS of 5.3, 8.1, and 14.8 months, respectively. PFS and OS for each patient showed a correlation of ρ = 0.75 [95 % confidence interval (CI) 0.69–0.81]. PPS and OS showed a correlation of ρ = 0.87 (95 % CI 0.84–0.91). According to multivariate analysis, performance status at progression, PFS of first-line chemotherapy, and use of second-line chemotherapy were independently associated with PPS.

Conclusions

These results indicate that both PFS and PPS are correlated with OS in first-line chemotherapy for AGC, suggesting the importance of reporting detailed patient characteristics and treatment course after disease progression in clinical trials of first-line chemotherapy for AGC.     

Efficacy of a Metallic Stent Covered with a Paclitaxel-Incorporated Membrane Versus a Covered Metal Stent for Malignant Biliary Obstruction: A Prospective Comparative Study

Background

The placement of a self-expandable metallic stent (SEMS) is a widely used nonsurgical treatment method in patients with unresectable malignant biliary obstructions but SEMS is susceptible to occlusion by tumor ingrowth or overgrowth.

Aim

The efficacy and safety of a metallic stent covered with a paclitaxel-incorporated membrane (MSCPM) in which paclitaxel provided an antitumoral effect was compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions.

Methods

Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. A MSCPM was inserted endoscopically in 60 patients, and a CMS was inserted in 46 patients. Patients underwent systemic chemotherapy regimens alternatively according to disease characteristics.

Results

The two groups did not differ significantly in mean age, male to female ratio, or mean follow-up period. Stent occlusion due to tumor ingrowth occurred in 12 patients who received MSCPMs and in eight patients who received CMSs. Stent patency and survival time did not differ significantly between the two groups (p = 0.116, 0.981). Chemotherapy had no influence on stent patency, but gemcitabine-based chemotherapy was a significant prognostic factor for survival time (p = 0.012). Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups.

Conclusions

Although the use of a MSCPM produced no significant differences in stent patency or patient survival in patients with malignant biliary obstructions compared with the use of a CMS, this study demonstrated that MSCPM can be used safely in humans.     

Increased Rates of Duodenal Obstruction in Pancreatic Cancer Patients Receiving Modern Medical Management

Background

Duodenal obstruction from pancreatic cancer historically occurs in 2–25 % of patients without surgery, but with new advances in chemotherapy and radiation therapy, the life expectancy of pancreatic cancer has increased.

Aim

The aim of the study was to determine the rate of development of duodenal obstruction requiring intervention in patients with pancreatic head adenocarcinoma who do not undergo surgical resection, but receive modern chemoradiation.

Methods

It is a retrospective single center study. Inclusion criteria were patients with pancreatic cancer who underwent ERCP with metal biliary stent and then chemoradiation who subsequently developed symptomatic duodenal obstruction and underwent either metal duodenal stent placement or surgical duodenal bypass.

Results

Twenty-four of 63 patients (38 %, 95 % CI 26–50 %) with unresectable pancreatic cancer and biliary stents who received chemotherapy and/or radiation therapy developed duodenal obstruction. The average length of time from diagnosis of pancreatic adenocarcinoma to development of outlet obstruction was 11.4 ± 4.9 months (range 1.5–40 months). Average length of time from development of duodenal obstruction to death was 4.8 ± 2.1 months (range 0.5–60 months). Average survival time from diagnosis to death was 16.6 ± 5.6 months (range 4.5–58 months).

Conclusion

Thirty-eight percent of patients with unresectable pancreatic head adenocarcinoma and metal biliary stents who receive chemotherapy and/or radiation therapy eventually develop symptomatic duodenal obstruction requiring duodenal stent or surgical bypass. This rate of duodenal obstruction is nearly twice that of previous reports using older oncologic therapy and will likely increase as patients survive longer with advances in medical therapy for pancreatic cancer.     

Role of adjuvant surgery for patients with initially unresectable pancreatic cancer with a long-term favorable response to non-surgical anti-cancer treatments: results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery

Purpose

A multicenter survey was conducted to explore the role of adjuvant surgery for initially unresectable pancreatic cancer with a long-term favorable response to non-surgical cancer treatments.

Methods

Clinical data including overall survival were retrospectively compared between 58 initially unresectable pancreatic cancer patients who underwent adjuvant surgery with a favorable response to non-surgical cancer treatments over 6 months after the initial treatment and 101 patients who did not undergo adjuvant surgery because of either unchanged unresectability, a poor performance status, and/or the patients’ or surgeons’ wishes.

Results

Overall mortality and morbidity were 1.7 and 47 % in the adjuvant surgery group. The survival curve in the adjuvant surgery group was significantly better than in the control group (p < 0.0001). The propensity score analysis revealed that adjuvant surgery was a significant independent prognostic variable with an adjusted hazard ratio (95 % confidence interval) of 0.569 (0.36–0.89). Subgroup analysis according to the time from initial treatment to surgical resection showed a significant favorable difference in the overall survival in patients who underwent adjuvant surgery over 240 days after the initial treatment.

Conclusion

Adjuvant surgery for initially unresectable pancreatic cancer patients can be a safe and effective treatment. The overall survival rate from the initial treatment is extremely high, especially in patients who received non-surgical anti-cancer treatment for more than 240 days.     

Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

Background

Platinum and 5-fluorouracil (5-FU)-based regimens have been used the most frequently in palliative chemotherapy for gastric cancer. The present study evaluated the prognostic significance of Bax, excision repair cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) in advanced gastric cancer patients treated with 5-FU, leucovorin, and oxaliplatin (FOLFOX) palliative chemotherapy.

Methods

Seventy-two patients with metastatic or recurrent gastric cancer were treated with FOLFOX regimen. Pretreatment tumor biopsy specimens were analyzed for Bax, ERCC1, and TS expression by immunohistochemistry.

Results

High expression of Bax, ERCC1, and TS was observed in 31 (43%), 33 (46%), and 35 (49%) patients, respectively. The median overall survival (OS) of patients was 12 months. Low expression of Bax was associated with poor OS (median, 9 months vs. 18 months; 2-year, 10% vs. 48%; p = 0.0005) in univariate analysis, while expression of ERCC1 and TS was not correlated with patient outcome. In multivariate analysis, low expression of Bax was a significant independent predictor of poor OS (p = 0.028). Low expression of Bax was significantly associated with poor survival of patients with metastatic or recurrent gastric cancer treated with FOLFOX chemotherapy.

Conclusions

Immunohistochemical staining for Bax with pretreatment biopsy specimen may be useful in selecting FOLFOX regimen as a treatment option for advanced gastric cancer patients.     

A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer

Background/purpose

S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80?mg/m²/day given on days 1?C21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).

Methods

Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0?C1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4?weeks of chemoradiotherapy. S-1 was given orally at a dose of 80?mg/m²/day twice daily on days 1?C21. Radiotherapy was delivered in fractions of 1.25?Gy twice daily, 5?days per week for 4?weeks (total dose: 50?Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14?days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.

Results

Fifty patients were enrolled in this phase II study. Median follow-up was 14.6?months (range 5.4?C58.9?months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18?C45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7?months (95% CI, 4.7?C11.2?months) and 14.3?months (95% CI, 10.8?C20.8?months), respectively. Survival rates at 1 and 2?years were 62 and 27%, respectively.

Conclusions

Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.