Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis.

Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated to play a critical role in the expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, leading to production of mature myeloid cells, although their inhibitory effects on hematopoiesis were also reported. Therefore, the molecular mechanism of emergency myelopoiesis during infection remains incompletely understood. Here, we clarify that one of the interleukin (IL)-6/IL-12 family cytokines, IL-27, plays an important role in the emergency myelopoiesis. Among various types of hematopoietic cells in bone marrow, IL-27 predominantly and continuously promoted the expansion of only Lineage-Sca-1+c-Kit+ (LSK) cells, especially long-term repopulating HSCs and myeloid-restricted progenitor cells with long-term repopulating activity, and the differentiation into myeloid progenitors in synergy with stem cell factor. These progenitors expressed myeloid transcription factors such as Spi1, Gfi1, and Cebpa/b through activation of signal transducer and activator of transcription 1 and 3, and had enhanced potential to differentiate into migratory dendritic cells (DCs), neutrophils, and mast cells, and less so into macrophages, and basophils, but not into plasmacytoid DCs, conventional DCs, T cells, and B cells. Among various cytokines, IL-27 in synergy with the stem cell factor had the strongest ability to augment the expansion of LSK cells and their differentiation into myeloid progenitors retaining the LSK phenotype over a long period of time. The experiments using mice deficient for one of IL-27 receptor subunits, WSX-1, and IFN-γ revealed that the blood stage of malaria infection enhanced IL-27 expression through IFN-γ production, and the IL-27 then promoted the expansion of LSK cells, differentiating and mobilizing them into spleen, resulting in enhanced production of neutrophils to control the infection. Thus, IL-27 is one of the limited unique cytokines directly acting on HSCs to promote differentiation into myeloid progenitors during emergency myelopoiesis.

Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells.

Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.

Potential clinical application of interleukin-27 as an antitumor agent.

Cancer immunotherapies such as sipuleucel-T and ipilimumab are promising new treatments that harness the power of the immune system to fight cancer and achieve long-lasting remission. Interleukin (IL)-27, a member of the IL-12 heterodimeric cytokine family, has pleiotropic functions in the regulation of immune responses with both pro-inflammatory and anti-inflammatory properties. Evidence obtained using a variety of preclinical mouse models indicates that IL-27 possesses potent antitumor activity against various types of tumors through multiple mechanisms without apparent adverse effects. These mechanisms include those mediated not only by CD8(+) T cells, natural killer cells and macrophages, but also by antibody-dependent cell-mediated cytotoxicity, antiangiogenesis, direct antiproliferative effects, inhibition of expression of cyclooxygenase-2 and prostaglandin E2 , and suppression of epithelial-mesenchymal transition, depending on the characteristics of individual tumors. However, the endogenous role of IL-27 subunits and one of its receptor subunits, WSX-1, in the susceptibility to tumor development after transplantation of tumor cell lines or endogenously arising tumors seems to be more complicated. IL-27 functions as a double-edged sword: IL-27 increases IL-10 production and the expression of programmed death ligand 1 and T-cell immunoglobulin and mucin domain-3, and promotes the generation of regulatory T cells, and IL-27 receptor α singling enhances transformation; IL-27 may augment protumor effects as well. Here, we review both facets of IL-27, antitumor effects and protumor effects, and discuss the potential clinical application of IL-27 as an antitumor agent.

Critical role of p38 and GATA3 in natural helper cell function.

Natural helper (NH) cells, a member of Lin(-)IL-2R(+)IL-7R(+)IL-25R(+)IL-33R(+)GATA3(+) group 2 innate lymphoid cell subset, are characterized by the expression of transcription factors GATA3 and RORα and production of large amounts of Th2 cytokines such as IL-5, IL-6, and IL-13 upon IL-33 stimulation or a combination of IL-2 and IL-25. We have studied the signal transduction pathways critical for the cytokine expression and development of NH cell. Either stimulation with IL-33 or a combination of IL-2 and IL-25 induced p38 activation and phosphorylation of GATA3 in NH cells, and the phosphorylated form of GATA3 bound to the IL-5 and IL-13 promoters. All these events were blocked by SB203580, a p38 inhibitor. Inhibition of p38 also blocked IL-6 production. The mature NH cells lacking Gata3 were impaired in the proliferation and production of IL-5 and IL-13, but not IL-6, indicating that both p38 and GATA3 are critical for the proliferation and production of IL-5 and IL-13 and that the mechanisms downstream of p38 differ between IL-6 and IL-5/IL-13. In contrast, the NH cells lacking RORα showed no impairment in the proliferation and cytokine production, indicating that GATA3 but not RORα plays a pivotal role in the effector functions of mature NH cell. However, deletion of either GATA3 or RORα in hematopoietic stem cells severely blocked the development into NH cells. Our results demonstrate the important roles of p38 and GATA3 in NH cell functions.

Clinical outcomes of weekly cisplatin chemoradiotherapy for patients with pyriform sinus cancer.

BACKGROUND: Pyriform sinus squamous cell carcinoma (SCC) has one of the worst prognoses of all upper aerodigestive tract cancers. Improving clinical outcomes for patients with hypopharyngeal SCC has been particularly challenging for head and neck surgeons and oncologists. METHODS: We investigated 30 patients with pyriform sinus SCC to verify the effectiveness of weekly cisplatin chemotherapy with concurrent radiotherapy. Cisplatin was administered at a dose of 40 mg/m(2) on weeks 1, 2, 3, 5, 6, and 7 during definitive radiotherapy with the aim of preserving the larynx. RESULTS: All 30 patients achieved definitive radiotherapy at a median dose of 70 Gy (range 64-70 Gy). Cisplatin was administrated concomitantly a median of five times (range 2-6 times). Persistent or recurrent primary disease was observed in four patients (13 %). Persistent or recurrent nodal metastasis was observed in five patients (17 %). Nine salvage surgeries were performed for eight patients, of whom seven survived without any evidence of disease. Post-operative complications were observed in two patients (22 %). The 5-year overall survival and locoregional control rates were 87 and 96 %, respectively. The 5-year laryngeal preservation rate was 74 %. CONCLUSIONS: The regimen of weekly cisplatin CRT may be effective for pyriform sinus SCC; however, there were problems with strong selection bias in the current study due to the large number of T2 patients. Salvage surgery was safe and was able to improve the survival rate. This chemoradiation regimen was considered successful in preserving laryngeal function.

Early and long-term morbidity after minimally invasive total laryngo-pharyngo-esophagectomy with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision.

Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.

The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation.

The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3% (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2% (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.

Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases.

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF- α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

Combined modality therapy for laryngeal cancer with superselective intra-arterial cisplatin infusion and concomitant radiotherapy.

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

Long-Term Management of Incidental Bladder Cancer Detected in Patients Undergoing Prostatectomy for Prostate Cancer.

INTRODUCTION: At our institution, screening for incidental bladder cancer is routinely performed to avoid tumor cell dissemination caused by surgery in patients undergoing prostatectomy for prostate cancer (PCa). Here, we report the long-term clinical results in patients with incidental bladder cancer detected by routine screening prior to prostatectomy. MATERIALS AND METHODS: Between January 2003 and December 2013, 430 patients undergoing prostatectomy for resection of PCa were enrolled in this cohort study. All patients underwent screening with cystoscopy, urinary sediment analysis, and urinary cytology to detect incidental bladder cancer. The clinical outcomes of cases with incidental bladder cancer were evaluated. RESULTS: The incidence of incidental bladder cancer was 2.1% (9/430). All tumors were single papillary tumors located around the urinary orifice or lateral side and were diagnosed as urothelial cancer (UC). No significant findings were detected by urinary sediment analysis or urinary cytology. Pathological results of transurethral resections revealed 5 cases of pTa with Grade 1 UC and 4 cases of pTa with Grade 2 UC. Androgen-deprivation therapy was administered to 8/9 patients. During the observation period (average of 7.2 years), UC recurrence was detected in 2 cases (2 and 7.3 years). However, transurethral resection successfully removed the tumor completely. After an average of 19.6 months (12-25 months) without UC recurrence, 7 patients (77.8%) underwent prostatectomy, and 2 patients received radiation or androgen-deprivation therapy. Prostatectomy was carried out without dissemination of UC during the observation period. CONCLUSION: Incidental UC was detected in 2.1% of prostatectomy candidates. Preoperative routine screening with flexible cystoscopy was useful to detect early incidental UC.

Optimal Monitoring of Prostate-Specific Antigen Detects Prostate Cancer at the Localized Stage after Photoselective Vaporization for Benign Prostatic Hyperplasia.

INTRODUCTION: Photoselective vaporization of the prostate (PVP) does not provide prostate tissue for pathologic analysis. Here, we carried out early monitoring for prostate cancer by measuring prostate-specific antigen (PSA) levels and assessing clinicopathological features after PVP. MATERIALS AND METHODS: Patients (n = 800) who underwent PVP and were followed-up for more than 12 months were analyzed retrospectively. After PVP, PSA levels were measured at 3 and 12 months and each year thereafter. Prostate biopsies were performed when PSA levels increased continuously. We assessed the characteristics of patients diagnosed with prostate cancer. RESULTS: The mean follow-up period was 49 months. After PVP, 54 patients underwent biopsies, and 23 patients were diagnosed with prostate cancer. Overall, 10, 10, and 3 patients had clinical stage T1c, T2a, and T2b disease, respectively, and there were no cases of stage T2c disease or greater. CONCLUSIONS: We found that it was possible to diagnose prostate cancer at a localized stage under our optimal PSA monitoring schedule before and after PVP.

The GP Score, a Simplified Formula (Bioptic Gleason Score Times Prostate Specific Antigen) as a Predictor for Biochemical Failure after Prostatectomy in Prostate Cancer.

OBJECTIVES: We used a new GP score (Gleason score multiplied by prostate-specific antigen) without the T stage as a predictive value for biochemical failure (BCF) after prostatectomy. MATERIALS AND METHODS: We assessed 459 prostate cancer patients who underwent prostatectomies at our institution. Three sub-groups were defined in terms of D'Amico classification risk (low, intermediate, and high) and Gleason score (low, < 50; intermediate, 50-100; and high GP score, > 100). Risk factors for BCF were evaluated by multivariate analysis with a Cox hazard model. A log-rank test was used to compare the BCF rate in the 2 groups. RESULTS: There was nosignificant difference in the non-BCF rate between the lowrisk and low GP score subgroups or the intermediate risk andintermediate GP score subgroups. In contrast, the non-BCFrate of the high GP score subgroup (42.1%) was significantlylower than that of the high-risk subgroup (66.1%, log-rankp = 0.008). Based on multivariate analysis, a high GP score(p = 0.001; HR 3.78; 95%CI 1.95-7.35) was a significant independent risk factor for BCF after prostatectomy. CONCLUSION: The GP score, consisting of two absolute numbers, may be a valuable predictive factor for BCF after prostatectomy, especially in the high-risk failure group.

Evaluation to Differentiate between Tumor Lesions and the Parenchyma in Partial Nephrectomies for Renal Tumors Based on Quantitative Fluorescence Imaging Using Indocyanine Green Dye.

INTRODUCTION: Near-infrared fluorescence imaging with indocyanine green is a useful tool during partial nephrectomy. Because an accurate method for judging hasn't been established yet, the success rate may be slightly different and inconsistent. MATERIALS AND METHODS: A total of 21 cases with suspected renal cancers who had undergone a partial nephrectomy were enrolled. We examined differences in the success rate between malignant lesions and the parenchyma by quantifying fluorescence in the pre-resection and ex vivo phases. RESULTS: Pre-resection imaging showed a significant degradation of fluorescence in the focused lesion in 76.2% (16/21) of cases. A significant degradation was observed in 73.7% (14/19) of the total malignant lesions, 70.5% (12/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. In contrast, imaging of the ex vivo resected specimens showed a significant degradation in fluorescence of the focused lesions in 85.7% (18/21) of cases. A significantly degradation was observed in 84.2% (16/19) of the total malignant lesions, 82.3% (14/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. CONCLUSION: We firstly evaluated the efficacy of quantitative indocyanine green-based fluorescence as an objective method.

Favorable 10-year outcomes of image-guided intensity-modulated radiotherapy combined with long-term androgen deprivation for Japanese patients with nonmetastatic prostate cancer.

AIM: To investigate 10-year outcomes of high-dose image-guided intensity-modulated radiation therapy (IG-IMRT) combined with long-term androgen deprivation therapy (ADT) for Japanese patients with nonmetastatic prostate cancer. METHODS: A retrospective analysis was performed on 208 Japanese patients with T1-4N0M0 prostate cancer, who underwent definitive IG-IMRT from 2006 to 2010 at our single institution. The median dose was 78 Gy (74-78) and median ADT time was 32 months (6-151). The risk stratification followed the National Comprehensive Cancer Network criteria. A biochemical relapse was defined as nadir plus 2.0 ng/mL. Toxicity was scored with the Radiation Therapy Oncology Group morbidity scale. RESULTS: The median follow-up time was 102 months. For low-, intermediate-, high-, and very-high-risk groups, the 10-year biochemical disease-free survival rates were 100%, 84%, 90%, and 72%, respectively (P = 0.008); clinical relapse-free survival rates were 100%, 100%, 100%, and 81%, respectively (P < 0.001); and cancer-specific survival rates were 100%, 100%, 100%, and 89%, respectively (P = 0.13). The independent prognostic factors influencing biochemical relapse were younger age, Gleason score ≥ 8, and radiation dose < 78 Gy in the multivariate analysis (P = 0.006, 0.014, and 0.013). The 10-year cumulative incidence of late grade 2 or higher gastrointestinal and genitourinary toxicities were 12% and 13%, respectively. No events of grade 4 or 5 were observed. CONCLUSIONS: This study suggest that high-dose IG-IMRT combined with long-term ADT is effective and implementable, leading to excellent 10-year outcomes for Japanese patients with nonmetastatic prostate cancer.

Initial CT findings in early tongue and oral floor cancer as predictors of late neck metastasis.

Detecting the risk factors for late neck metastasis (LNM) in early tongue and oral floor cancer is important for establishing an accurate prognosis, as well as for increasing survival rates. Patients with either stage I or II tongue and oral floor cancer underwent either a resection of the primary tumor or interstitial radiotherapy without neck dissection. We measured the short- and long-axis diameters of lymph nodes on initial CT images. Of the 38 patients, 20 had LNM and 18 did not. CT images showed a total of 161 lymph nodes. Twenty-five "occult lymph nodes" developed into LNM, whereas the remaining 136 "reactive lymph nodes" did not. Comparison between "occult" and "reactive" lymph nodes revealed significant differences in the short-axis diameters (p=0.01). The measure of short-axis diameters of neck lymph nodes on initial CT images is a useful predictor of LNM in patients with early tongue and oral floor cancer.

Effects of dose-escalated radiotherapy in combination with long-term androgen deprivation on prostate cancer.

OBJECTIVE: We aimed to examine the effects of a dose escalation for prostate cancer patients receiving long-term androgen deprivation therapy (ADT). METHODS: A retrospective analysis of 605 patients treated with radiotherapy (RT) and long-term ADT (National Comprehensive Cancer Network criteria-defined intermediate-risk, minimum 10 months; high-risk and very-high-risk, minimum 20 months) was performed. The median ADT time was 31 months. Cox's proportional hazards models were used to compare biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and overall survival (OS) between the ≥70, <78 Gy group and 78 Gy group in a univariate analysis and to assess the effects of the dose escalation on bDFS in a multivariate analysis. RESULTS: After a median follow-up of 70 months, 5-year bDFS was significantly better in the 78 Gy group than in the ≥70, <78 Gy group [96 vs 83%; hazard ratio 3.6 (95% confidence interval 2.2-6.1); p < 0.001]. 5-year cRFS and OS were similar between the two groups. The multivariate analysis showed that RT dose was still an independent prognostic factor of bDFS (p = 0.005). CONCLUSION: The results of the present study suggest that dose escalations result in significant improvements in bDFS, even when used in combination with long-term ADT. A longer follow-up is needed to clarify the effects of dose escalations on cRFS and OS. Advances in knowledge: It remains unclear whether high-dose RT is necessary for improving the outcomes of patients receiving long-term ADT. The results suggest that dose escalations result in significant improvements in biochemical control.

Photoselective Vaporization of the Prostate: Long-Term Outcomes and Safety During 10 Years of Follow-Up.

PURPOSE: To evaluate the long-term outcomes and safety photoselective vaporization of the prostate (PVP). PATIENTS AND METHODS: From April 2005 to December 2015, a total of 1154 patients with benign prostatic hyperplasia underwent PVP. The type of Green Light laser was an 80 W potassium-titanyl-phosphate laser and later a 120 W lithium triborate laser. Before and after surgery, the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), post-voiding volume of residual urine (PVR), prostate-specific antigen (PSA) level, and prostate volume were assessed regularly. After surgery, events such as second PVP, transurethral incision, and permanent urethral catheterization were defined as retreatment. RESULTS: The mean and median periods of follow-up after PVP were 35.4 and 24.0 months, respectively. The maximum duration of follow-up was 125 months. Compared with before surgery, the IPSS, quality of life score, and PSA concentration improved significantly, even at 10 years after PVP; however, Qmax and PVR were not improved at 10 years. The retreatment-free survival rate was 93.9% at 5 years and 79.0% at 10 years. Prostate cancer was found in 27 cases after PVP, and all patients who were found to have prostate cancer remained alive. Prostate cancer-free survival after PVP was 96.7% at 5 years and 89.4% at 10 years. CONCLUSION: Our data suggest that the efficacy of PVP was maintained for 10 years; however, it may decrease after more than 10 years. PVP also did not promote the progression of or worsen the prognosis of prostate cancer.

Therapeutic potential of interleukin-27 against cancers in preclinical mouse models.

Since we first reported the antitumor efficacy of IL-27 in 2004, accumulating evidence obtained by several groups using a variety of preclinical mouse models indicates that IL-27 possesses potent antitumor activity against various types of tumors through multiple mechanisms depending on the characteristics of individual tumors without apparent adverse effects.

Comparison of acute toxicities associated with cetuximab-based bioradiotherapy and platinum-based chemoradiotherapy for head and neck squamous cell carcinomas: A single-institution retrospective study in Japan.

CONCLUSION: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. OBJECTIVES: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. METHOD: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m(2) was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m(2) of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m(2) weekly during the definitive radiotherapy. RESULTS: The BRT group had a higher incidence of Grade ≥ 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade ≥ 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).

Indications for superselective intra-arterial cisplatin infusion and concomitant radiotherapy in cases of hypopharyngeal cancer.

OBJECTIVE: We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC). METHODS: Between April 2000 and March 2013, 41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70Gy). RESULTS: During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 (n=14) and N2b-3 disease (n=27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease (n=3) died of disease within 2 years. CONCLUSION: Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1.