Showing papers in "International Journal of Clinical Oncology in 2014"

Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials.

Abstract: Aims The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab.

Current status of oral cancer treatment strategies: surgical treatments for oral squamous cell carcinoma

Abstract: The primary treatment modality of oral cancer is generally determined according to the stage of the disease, with surgical treatment remaining the mainstay of multimodal treatment. When selecting the treatment, many factors are taken into consideration, and the treatment should be tailored individually to the patient’s needs and consider the quality of life as well as the survival of the patient. Early-stage disease is primarily managed with surgery or brachytherapy without functional morbidity, whereas for advanced-stage disease multidisciplinary treatment is recommended, not only for enhanced survival but also for improved quality of life. After resection of large primary tumors, reconstructive surgery is required. Free tissue transfer currently represents one of the most popular and reliable techniques for oral reconstruction. For cN0 neck, elective neck dissection is recommended when the risk of occult metastases is >20 %, when the neck is entered either for resection of the primary tumor or for reconstruction, or when the patient is unlikely to return for a close follow-up. Sentinel node biopsy is performed investigationally. Modified radical neck dissection is the gold standard for cN+ neck. For patients with multiple node metastases or extracapsular spread, postoperative radiotherapy or chemoradiotherapy is recommended, with the lymph nodes situated outside the confines of the radical neck dissection, such as the lingual and retropharyngeal nodes, receiving considerable attention. Targeted therapy for oral cancer is still a relatively new concept, and more studies are needed to confirm the clinical effectiveness of these drugs.

Radiobiological basis of SBRT and SRS.

Abstract: Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) have been demonstrated to be highly effective for a variety of tumors. However, the radiobiological principles of SBRT and SRS have not yet been clearly defined. It is well known that newly formed tumor blood vessels are fragile and extremely sensitive to ionizing radiation. Various lines of evidence indicate that irradiation of tumors with high dose per fraction, i.e. >10 Gy per fraction, not only kills tumor cells but also causes significant damage in tumor vasculatures. Such vascular damage and ensuing deterioration of the intratumor environment then cause ischemic or indirect/secondary tumor cell death within a few days after radiation exposure, indicating that vascular damage plays an important role in the response of tumors to SBRT and SRS. Indications are that the extensive tumor cell death due to the direct effect of radiation on tumor cells and the secondary effect through vascular damage may lead to massive release of tumor-associated antigens and various pro-inflammatory cytokines, thereby triggering an anti-tumor immune response. However, the precise role of immune assault on tumor cells in SBRT and SRS has not yet been clearly defined. The “4 Rs” for conventional fractionated radiotherapy do not include indirect cell death and thus 4 Rs cannot account for the effective tumor control by SBRT and SRS. The linear-quadratic model is for cell death caused by DNA breaks and thus the usefulness of this model for ablative high-dose SBRT and SRS is limited.

CD133 expression: a potential prognostic marker for non-small cell lung cancers.

Abstract: Background CD133 is a membrane glycoprotein containing five transmembrane loops. Previous reports suggest that a CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal characteristics has biological features of a cancer stem cell. In addition, the presence of CD133-positive cells was associated with a significantly poorer prognosis for some solid tumors, compared to those with CD133-negative cells. However, the clinicopathological significance of CD133 in non-small cell lung cancer (NSCLC) remains controversial.

Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer

Abstract: There are many complex and rare mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) other than the two classical mutations of L858R and exon 19 deletional mutation. The purpose of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs). We analyzed 1,431 NSCLC patients who were treated with either gefitinib or erlotinib. Exons 18 to 21 of EGFR were analyzed by PCR and subjected to direct sequencing methods. Of 306 patients who had EGFR mutation, 24 patients (7.3 %) had complex mutations. The frequency of rare mutations was 10.3 %. Four groups were categorized [group A (N = 269): classical mutation alone; group B (N = 16): complex mutation with classical mutation; group C (N = 16): rare mutation alone or complex mutation with rare mutation; group D (N = 5); classical mutation with T790M]; the response rate (RR) to TKI was significantly different between each group (RR = 74.8 % in group A vs. 68.8 % in group B vs. 25.0 % in group C vs. 80.0 % in group D, P < 0.001). Progression-free survival (PFS) was also poorer in rare mutations (median PFS: 11.9 vs. 8.1 vs. 1.4 vs. 8.0 months, respectively, P < 0.001). NSCLC patients harboring rare mutations did not show consistent and favorable responses to EGFR TKI compared with those harboring classical mutations. However, complex mutations with classical mutations showed similar treatment efficacy toward EGFR TKI to that with classical mutations alone.

Update of molecular pathobiology in oral cancer: a review

Abstract: Head and neck cancer including oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. OSCC has a high potential for local invasion and nodal metastasis, and the overall 5-year survival rate has not significantly changed during the past 30 years. Recent research has elucidated the detailed molecular mechanisms of carcinogenesis, tumor progression, and metastasis of OSCC. It is generally accepted that OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens such as alcohol, smoking, viral infections, and inflammation. The molecular mechanisms of carcinogenesis, tumor progression, and metastasis of head and neck cancer have been elucidated by recent advances in molecular biology. However, many unsolved questions remain. In this review, we describe the current molecular biological findings such as human papillomavirus infection, epithelial–mesenchymal transition, microRNA, and our novel molecular pathological findings of OSCC.

Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker

Abstract: Background Plasma amino acid profiles (PAAPs) vary in individual cancer patients, and it has been suggested that they may be useful for early detection of several types of cancer. We evaluated the diagnostic performance of a profile index for endometrial cancer composed of multiple plasma amino acids as a novel biomarker and compared its diagnostic performance with that of CA125.

Massage interventions and treatment-related side effects of breast cancer: a systematic review and meta-analysis.

Abstract: Massage as a complementary and alternative therapy has been associated with enhancing health and coping with treatment-related side effects in patients with breast cancer worldwide. This systematic review examined whether massage interventions provide any measurable benefit in breast cancer-related symptoms. Randomized controlled trials (RCTs) were searched for in PubMed, EMBASE.com and the Cochrane Library through June 2013. We evaluated the quality of the studies included by the Cochrane Handbook 5.2 standards and analyzed the data using the Cochrane Collaboration’s RevMan 5.2 software. Eighteen RCTs with a total of 950 participants were included. Compared with the control group, our meta-analysis showed that patients receiving regular use of massage had significantly greater reductions in anger and fatigue symptoms. However, there were no significant differences in depression, anxiety, pain, upper limb lymphedema, cortisol and health-related quality of life. The current evidence demonstrates that there was mild evidence that massage may be a useful intervention in alleviating negative emotions and fatigue in patients with breast cancer. More trials with longer follow-up are needed to determine the exact long-term efficacy of this class of complementary and alternative medicine on breast cancer-related symptoms and quality of life.

Clinical variables for predicting metastatic renal cell carcinoma patients who might not benefit from cytoreductive nephrectomy: neutrophil-to-lymphocyte ratio and performance status

Abstract: Cytoreductive nephrectomy (CN) plays an important role in the multimodal treatment of metastatic renal cell carcinoma (RCC). However, certain patients experience rapid progression of the carcinoma following CN. This study aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR) in the selection of patients for CN. Records corresponding to 73 patients with metastatic RCC were retrospectively reviewed. Forty-eight patients underwent CN, and their overall survival (OS) and preoperative variables were analyzed. The OS of patients who did not undergo CN was used as a reference. Univariate analysis showed that symptomatic tumors, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥1, hemoglobin level <12 g/dl, neutrophil count ≥5500/μL, C-reactive protein level ≥2.0 mg/dl, and NLR ≥4.0 were significantly associated with poor outcomes in patients who underwent cytoreductive nephrectomy. The median OS of patients with NLR ≥4.0 was 10.2 months, which was significantly shorter than that of patients with NLR <4.0 (36.5 months) (P = 0.0020). Multivariate analysis showed that NLR and ECOG-PS were independent predictors of OS in patients treated with CN. The OS of CN patients with NLR ≥4.0 and ECOG-PS ≥1 was similar to that of patients who did not undergo CN (8.4 vs. 6.1 months, P = 0.939). Preoperative NLR elevation is significantly associated with poor outcomes in patients with metastatic RCC who underwent CN. Patients with NLR ≥4.0 and ECOG-PS ≥1 might not benefit from immediate CN after initial diagnosis.

Evaluating the 21-gene assay Recurrence Score® as a predictor of clinical response to 24 weeks of neoadjuvant exemestane in estrogen receptor-positive breast cancer

Abstract: The aim of this study was to investigate the association between the results of the Recurrence Score (RS) assay and the clinical response to neoadjuvant endocrine therapy in postmenopausal women with breast cancer. Core biopsy samples at baseline and post-treatment surgical samples were obtained from 80 and 77 of 116 patients, respectively, enrolled in the multicenter prospective study of neoadjuvant exemestane therapy (JFMC34-0601). The 21-gene assay was performed after appropriate manual microdissection. The estrogen receptor (ER), progesterone receptor, HER2 and Ki-67 were assayed by immunohistochemistry at a central laboratory. Clinical response was assessed based on the RECIST (Response Evaluation Criteria In Solid Tumors) guideline. Sixty-four core biopsy samples and 52 resection samples met the RS quality requirements. The clinical response rate in those patients with a low RS result (low RS group; 19/32, 59.4 %) was significantly higher than that in those patients with a high RS result (high RS group; 3/15, 20.0 %) (P = 0.015) and similar to that in patients with an intermediate RS result (intermediate RS group; 10/17, 58.8 %). The rates of breast-conserving surgery (BCS) were 90.6 % (29/32) in the low RS group, 76.5 % (13/17) in the intermediate RS group and 46.7 % (7/15) in the high RS group. The odds ratio for BCS adjusted for continuous baseline Ki-67 was 0.114 [95 % confidence interval (CI) 0.014–0.721; P = 0.028] between the high and low RS groups. RS values in pre-treatment samples were highly correlated with those in post-treatment samples (Spearman correlation coefficient 0.745, 95 % CI 0.592–0.846). Our results demonstrate the predictive value of the RS for clinical response to neoadjuvant exemestane therapy in postmenopausal women with ER-positive breast cancer.

Carcinoma of unknown primary with gastrointestinal profile: immunohistochemistry and survival data for this favorable subset.

Abstract: Carcinoma of unknown primary with a “gastrointestinal profile” is an emerging, favorable entity. Distinguishing this entity is of increasing significance given the progress in the treatment of colorectal cancer. 74 carcinoma of unknown primary (CUP) patients with CDX2+ tumors were chosen from the databases at M.D. Anderson and Sarah Cannon Cancer Centers between 2004 and 2010. Data on clinical and pathological characteristics including therapy and survival were recorded. 20 patients had ascites on presentation; the predominant sites of metastases included liver (30 %), carcinomatosis (50 %), and nodes (51 %). Based on immunohistochemistry, 2 cohorts were created: Cohort 1—“consistent with lower GI profile” included 34 patients [CDX-2+, CK20+, CK7−] and Cohort 2—“probable lower GI profile” included 40 patients [CDX2+, irrespective of CK7/CK20 status]. Excluding 6 outliers, Cohorts 1 and 2 had 32 and 36 patients, respectively; their median survivals were 37 and 21 months, respectively. On multivariate Cox regression analysis, only liver metastases were found to negatively influence survival. Our retrospective study provides encouraging indications that CUP patients with gastrointestinal profiles benefit from site-specific therapy. We recommend all CUP patients, especially those with abdominal nodes, isolated carcinomatosis or liver metastases, to undergo optimal immunohistochemistry (IHC) to check for a gastrointestinal profile of CUP.

Inhibition of Hsp90 and 70 sensitizes melanoma cells to hyperthermia using ferromagnetic particles with a low Curie temperature

Abstract: Heat shock protein (Hsp) 90 is a key regulator of various oncogene products and cell-signaling molecules, while Hsp70 protects against heat-induced apoptosis. We previously described a system in which hyperthermia was produced using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T c) of 43 °C to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, the antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor (quercetin) with FMP-mediated hyperthermia were examined. Expressions of Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMPs were then injected into the resultant tumors, and the mice were divided into groups treated with quercetin and/or 17DMAG with/without hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMPs increased and stabilized at the T c. The TUNEL method was used to determine whether hyperthermia induced apoptosis within tumors. In the group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor growth was significantly suppressed 20 days after FMP injection in vivo, compared with other treatment groups. The survival rates among tumor-bearing mice observed for a period of 40 days were significantly higher in the hyperthermia + quercetin + 17DMAG group. Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.

Limitation of indocyanine green fluorescence in identifying sentinel lymph node prior to skin incision in cutaneous melanoma

Abstract: Although several reports have discussed the potential of the indocyanine green (ICG) fluorescence technique, its effectiveness and limitations have not been fully evaluated. For the accurate detection of sentinel lymph node (SLN) in cutaneous melanoma, which can arise in a wide variety of sites throughout the body, it is important to detect the SLN sites prior to skin incision. The purpose of this study was to evaluate the ICG fluorescence technique in the preoperative setting. We classified the detection process of SLN biopsy into three surgical stages: ‘before skin incision,’ ‘after skin incision,’ and ‘ex vivo.’ We retrospectively reviewed 93 node fields in 86 patients who underwent SLN biopsies using ICG and conventional techniques. The detection rate using ICG at the ‘before skin incision,’ ‘after skin incision,’ and ‘ex vivo’ surgical stages were 63.4, 98.9, and 100 %, respectively. At the ‘before skin incision’ surgical stage, while lymphoscintigraphy (but not ICG) detected 33 node fields, ICG (but not lymphoscintigraphy) detected only four node fields. The detection rates varied from 100 % in the groin region drained from trunk to 15.8 % in the axillary region from upper limb. The factors that influenced the failure of ICG to identify hot SLNs were an axillary node field (p < 0.001) and a high body mass index (BMI) (p = 0.046). For reliable identification of SLNs in cutaneous melanoma, the ICG fluorescence technique may offer little benefit for patients with axillary node field drained from upper limb, or high BMI.

Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma.

Abstract: Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer. The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels. The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues. Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis.

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer.

Abstract: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m2. Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m2 in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28–0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07–0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02–0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01–0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03–0.85; interaction, P = 0.13). Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.

DBC1 is over-expressed and associated with poor prognosis in colorectal cancer.

Abstract: Deleted in breast cancer 1 (DBC1) was initially cloned from a region homozygously deleted in breast cancers, but its role in colorectal cancer remains unknown. The present study aims to examine the expression level of DBC1 and assess its prognostic value in human colorectal cancer. Immunohistochemical staining was performed to detect the expression level of DBC1 in a series of 186 colorectal cancer patients. Immunohistochemical staining results were analyzed and compared statistically with various clinicopathological characters and overall survival. Compared with the corresponding non-tumor tissues, a higher expression level of DBC1 was detected in colorectal cancer (P < 0.01). Tissue microarray analysis revealed that DBC1 expression is significantly associated with tumor histological grade, TNM stage and metastatic status (P < 0.01). Importantly, Kaplan–Meier analysis showed that DBC1 expression is associated with shorter overall survival (P < 0.01). Univariate Cox regression suggested that DBC1 expression, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival in colorectal cancer (P < 0.05). Multivariate Cox regression analysis indicated that DBC1 acts as an independent prognostic factor in colorectal cancer (P < 0.01). These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis.

Long-term changes in renal function outcomes following radical cystectomy and urinary diversion

Abstract: Background We analyzed long-term changes in the renal function of patients undergoing radical cystectomy and urinary diversion (UD).

Importance of uterine cervical cerclage to maintain a successful pregnancy for patients who undergo vaginal radical trachelectomy.

Abstract: Background We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT.

Idiopathic pulmonary fibrosis as a prognostic factor in non-small cell lung cancer

Abstract: Background We investigated the postoperative mortality and long-term survival of lung cancer patients with underlying idiopathic pulmonary fibrosis (IPF).

Prognostic predictors and spread patterns in adult ovarian granulosa cell tumors: a multicenter long-term follow-up study of 108 patients.

Abstract: To identify prognostic predictors and spread patterns in adult ovarian granulosa cell tumors (OGCTs). Available retrospective data of 108 OGCT patients managed at three centers between January 1, 1991 and December 31, 2010 were abstracted and analyzed. Stage distributions at diagnosis for stage I, II and III OGCT were 84.3, 5.4, and 9.3 %, respectively. Optimal cytoreduction with no macroscopically visible disease was achieved in 99/108 (91.6 %) patients. The median disease-free interval to first recurrence was 61 months. The overall 5- and 10-year survival rates were 93.3 and 90.9 %, respectively. Disease recurred in 18 (16.6 %) patients, and 8 (7.4 %) patients died of their disease. The first recurrence sites included the pelvic peritoneum (n = 10), liver/liver-capsule (n = 5), rectosigmoid colon (n = 4), retroperitoneal lymph nodes (n = 3), omentum (n = 3), small bowel mesenterium (n = 2), and vaginal cuff (n = 2). Multiple-site recurrence was observed in 9/18 (50 %) patients. Secondary cytoreduction requiring extensive surgery was performed in 14 patients with an optimality rate of 71.4 %. The remaining four patients received only chemotherapy. Multivisceral approaches, including pelvic peritonectomy (n = 9; 64.2 %), rectosigmoid resection (n = 3; 21.4 %), and segmental liver capsule resection (n = 2; 14.2 %) were performed more frequently during the secondary surgery. Definitive retroperitoneal lymph node metastasis rates at the initial and recurrent settings were 5.1 % (3/58) and 21.4 % (3/14), respectively. Both stage and residual tumor status were significantly associated with recurrence in univariate and multivariate analyses. Stage and residual tumor status are predictors of recurrence. Pelvic peritoneal, nodal and hepatic involvement, and multiple-site spread patterns requiring extensive cytoreductive surgery are likely associated with recurrence of OGCTs.

Ever-advancing chronic myeloid leukemia treatment.

Abstract: Treatment of chronic myeloid leukemia (CML) has been drastically changed by the emergence of the ABL tyrosine kinase inhibitor (TKI), imatinib mesylate. However, resistance and intolerance have frequently been reported, particularly in patients with advanced-stage disease. Point mutations within the ABL kinase domain that interfere with imatinib binding are the most critical cause of imatinib resistance. To overcome this resistance, four second-generation ATP competitive ABL TKIs, dasatinib, nilotinib, bosutinib and bafetinib, have been developed. Dasatinib and nilotinib also demonstrated higher efficacy than imatinib in previously untreated CML patients in chronic phase. Despite promising clinical results, the frequently observed mutant T315I is not effectively targeted by any of the second-generation ABL TKIs. Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harbouring T315I. CML treatment is rapidly progressing and further evolution is surely expected. Moreover, it was recently reported that some CML patients who achieved sustained complete molecular response could stop TKI. CML may become the first human cancer to be conquered solely with oral medicines.

Chemotherapy for extensive-stage small-cell lung cancer with idiopathic pulmonary fibrosis.

Abstract: Idiopathic pulmonary fibrosis (IPF) is associated with an independent increased risk of lung carcinogenesis. The benefit of chemotherapy for extensive-stage small-cell lung cancer (ED-SCLC) in cases of IPF remains unknown. This study was conducted to elucidate the efficacy of chemotherapy for ED-SCLC in patients with IPF. This was a retrospective observational study of ED-SCLC patients with IPF (all with distant metastasis) who received systemic chemotherapy. The response rate, toxicity, overall survival, and progression-free survival (PFS) were investigated. Eleven patients treated with chemotherapy between January 2005 and December 2011 were the subjects of this study. The overall response rate with the 1st regimen was 63.6 %. The median overall survival was 7.0 months, and the median PFS was 4.7 months. Our results suggest that ED-SCLC patients with IPF may benefit from chemotherapy. A prospective study will be needed to confirm this in the future.

Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck

Abstract: Boron neutron capture therapy (BNCT) is among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma. Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4. All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater. Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated.

Long-term oncological outcome in men with T3 prostate cancer: radical prostatectomy versus external-beam radiation therapy at a single institution.

Abstract: This study was designed to compare the long-term oncological outcome of patients with clinical T3 (cT3) prostate cancer (PCA) treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and to identify predictors of oncological outcomes. A total of 231 patients with cT3 PCA underwent either RP (n = 112) or EBRT (n = 119). Local progression-free (LPFS), distant metastasis-free (DMFS), cancer-specific (CSS), and overall survival curves were generated with the Kaplan–Meier method, and the differences in survival rates between the two groups were assessed with a log-rank test. Cox proportional stepwise multivariate analysis was used to assess the association of variables to the oncological outcomes. The median follow-up of the RP and EBRT groups was 93 and 85 months, respectively (p = 0.004).The 10-year LPFS, DMFS, and CSS rates were not statistically different between the two groups (90.2, 73.9, and 93.7 % in the RP group and 82.7, 88.2, and 85.1 % in the EBRT group; p = 0.25, 0.10, and 0.10, respectively). The Cox proportional multivariate analysis revealed that clinical T3b (cT3b) (p = 0.001) and a biopsy Gleason score of 7–10 (p = 0.043) were significant predictors of cancer-specific mortality and that cT3b was also a significant predictor of local progression and all-cause mortality. In cT3 PCA, both RP and EBRT provide an excellent long-term oncological outcome. cT3b was the strongest predictor of oncological outcome for the patients with locally advanced PCA who underwent the definitive therapy.

Subcellular localization of Mdm2 expression and prognosis of breast cancer

Abstract: Background Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53–Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53–Mdm2 in breast cancer remains unclear.

Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry

Abstract: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer. This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1–P3). Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors. Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.

Inverse Associations Between Serum Concentrations of Zeaxanthin and Other Carotenoids and Colorectal Neoplasm in Japanese

Abstract: Background To investigate the associations between serum concentrations of carotenoids and the presence of colorectal polyps and cancers in Japanese using a cross-sectional study.

Is biomarker research advancing in the era of personalized medicine for head and neck cancer

Abstract: Recent progress in molecular biology and translational research has initiated an era of personalized medicine in head and neck clinical oncology. The genetic information defined by biomarker analysis in tumors and individuals is indispensable for the administration of molecular targeting agents. The epidermal growth factor receptor (EGFR) signaling pathway is an important therapeutic target in head and neck squamous cell carcinoma (HNSCC). The use of an anti-EGFR monoclonal antibody (mAb), cetuximab (Cmab), has been approved for the treatment of patients with head and neck cancer. Although KRAS mutation has been established as a potential biomarker for predicting the efficacy of anti-EGFR mAb in colorectal cancer, little is known about predictive markers for Cmab in head and neck cancer. Optimal predictive and prognostic markers as well as safety markers are required to promote the appropriate clinical use of Cmab and to determine malignant phenotypes in head and neck cancer. This article first reviews the role of EGFR signaling in HNSCC. The article then focuses on Ras/Raf/Mek/Erk and PTEN/PI3K/Akt signaling pathways as predictive markers for Cmab. Subsequently, the molecular basis and clinical outcome of human papillomavirus (HPV)-positive cancer is highlighted, and the potential role of anti-EGFR target therapy for HPV-positive HNSCC is discussed. Finally, the possible mechanism for resistance to anti-EGFR target therapy is reviewed, and I discuss approaches to overcome the resistance with reference to an ongoing clinical trial.

Safety and efficacy of nimotuzumab in combination with radiotherapy for patients with squamous cell carcinoma of the esophagus.

Abstract: Background We investigated nimotuzumab (h-R3), a humanized monoclonal antibody against epidermal growth factor receptor, when combined with irradiation or chemoradiation for squamous cell carcinoma (SCC) of the esophagus. The aim of this study was to evaluate its safety and efficacy.

Sparing level Ib lymph nodes by intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma

Abstract: Background We retrospectively investigated the patterns of locoregional relapse and survival of patients to evaluate whether sparing level Ib lymph nodes by intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma was feasible.