Reduction in severity of radiation-induced dermatitis in head and neck cancer patients treated with topical aloe vera gel: A randomized multicenter double-blind placebo-controlled trial.

PURPOSE: To assess the efficacy of topical aloe vera gel on radiation induced dermatitis (RID) in head and neck cancer (HNC) patients. METHOD: In this multicenter randomized double-blind controlled study, HNC patients treated with concurrent chemoradiation (CCRT) received either aloe vera gel or placebo gel. Adverse skin toxicity levels were evaluated with the radiation-induced skin reaction assessment scale (RISRAS). RESULTS: One hundred-twenty patients were enrolled in this study. Analysis of the baseline characteristics did not reveal any differences between the groups. The median RISRAS values from the 1st to the 8th week of the CCRT course were not statistically different between the two groups. In the 5th and 6th weeks of treatment, moderate to severe grades of skin erythematous were observed at values of 13.6% and 24.1% versus 27.8 and 42.6% for members of the aloe vera gel group and the placebo group, respectively (p = 0.05 for the 5th week and p = 0.038 for the 6th week). In the 7th week, moderate to severe instances of moist desquamation were observed in eight patients (19.0%) in the placebo group (p = 0.001). Subjects experienced a burning sensation with RISRAS scores of 3-4 in the 7th week representing only 11.9% of patients in the placebo group (p = 0.016). CONCLUSION: Topical applications of aloe vera gel significantly reduced moderate to severe grades of skin erythematous and instances of moist desquamation in HNC patients receiving CCRT. In this study, there was no prophylactic efficacy for RID in the aloe vera gel group when compared to the placebo group.

Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer.

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.

Disparities in the change of cervical cancer mortality rate between urban and rural Chiang Mai in the era of universal health care and the Thai national screening program.

BACKGROUND: The Ministry of Public Health of Thailand established universal health coverage (UHC) in 2002, which also included national-level screening for cervical cancer in 2005. This study examined the changes in mortality of cervical cancer in rural and urban areas in Chiang Mai Province of northern Thailand during the era of UHC and the immediately preceding period. METHODS: Data of cervical cancer patients in Chiang Mai in northern Thailand, who died from 1998 through 2012, were used to calculate the change in age-standardized rates of mortality (ASMR) using a joinpoint regression model and to calculate estimated annual percent changes (APC). The change in mortality rate by age groups along with changes by geographic area of residence were determined. RESULTS: Among the 1177 patients who died from cervical cancer, 13(1%), 713 (61%) and 451 (38%) were in the young age group (aged < 30), the screening target group (aged 30-59) and the elderly group (aged ≥60), respectively. The mortality rate among women aged 30-59 significantly declined by 3% per year from 2003 through 2012 (p < 0.001). By area of residence, the mortality rate in women targeted by the screening program significantly decreased in urban areas but remained stable in more rural areas, APC of - 7.6 (95% CI: - 12.1 to - 2.8) and APC of 3.7 (95% CI: - 2.1 to 9.9), respectively. CONCLUSION: The UHC and national cervical cancer screening program in Thai women may have contributed to the reduction of the mortality rate of cervical cancer in the screening target age group. However, this reduction was primarily in urban areas of Chiang Mai, and there was no significant impact on mortality in more rural areas. These results suggest that the reasons for this disparity need to be further explored to equitably increase access to cervical cancer services of the UHC.

Dynamic changes in practical inflammation and immunity markers in cancer patients receiving immune-enhancing nutritional supplementation during concurrent chemoradiotherapy.

BACKGROUND: Immune-enhancing nutrition (IMN) strengthens the systematic inflammatory response and the immune system. Neutrophil to lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are affected during cancer therapies. OBJECTIVE: We carried out an analysis of the dynamic changes in NLR and ALC over time in cancer patients with or without IMN supplementation. METHODS: 88 cancer patients receiving concurrent chemoradiotherapy (CCRT) were randomized into regular diet group, and regular diet and IMN group.Generalized estimation equation models were used to assess associations between patient's characteristics, IMN, and dynamic changes in NLR and ALC over time. RESULTS: NLR and ALC at pre-CCRT were significantly associated with dynamic changes in NLR (adjusted ß= 1.08, 95% confidence interval [CI]: 0.64-1.52) and ALC (adjusted ß= 0.41, 95% CI: 0.36-0.46). The magnitudes of the NLR and ALC changes through CCRT were lower in patients receiving IMN, although the differences were not statistically significant except ALC at the end of CCRT in head and neck cancer patients (P= 0.023). CONCLUSION: Dynamic negative changes in both markers were demonstrated throughout CCRT. There were non-significant trend in promising changes in both NLR and ALC values in the whole group in IMN supplementation.

Two-year outcome of concurrent chemoradiation with carboplatin with or without adjuvant carboplatin/fluorouracil in nasopharyngeal cancer: A multicenter randomized trial.

BACKGROUND: According to the noninferiority result of chemoradiation with carboplatin in our previous nasopharyngeal carcinoma (NPC) study along with the inconclusive data on the efficacy of adjuvant chemotherapy (AC) following concurrent chemoradiotherapy (CCRT), we designed to assess the role of adjuvant carboplatin/fluorouracil following CCRT with carboplatin in locoregionally advanced NPC. MATERIALS AND METHODS: A multicenter randomized trial was conducted at 5 cancer centers in Thailand. We enrolled in stage T2N0M0-T4N2M0 (American Joint Cancer Committee 7th edition) WHO Type 2 NPC patients. N3 or metastatic disease patients were excluded. Participants were randomized into 2 groups: CCRT plus AC group vs the CCRT alone group. Patients in both groups received weekly carboplatin 100 mg/m2 for 6 cycles concurrently with radiotherapy 69.96-70 Gy. Patients in the AC group subsequently received 3 cycles of carboplatin area under curve-5 plus 1000 mg/m2/day of fluorouracil infusion within 96 hours every 3 weeks. We report the 2-year overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Treatment-related toxicities and compliance were also explored. RESULTS: Of 175 patients, 82 (46.9%) were assigned to the AC group, and 93 (53.1%) to the CCRT group. The compliance rate during CCRT was 90% and 86% in the AC and CCRT group, whereas 81.7% during adjuvant treatment in the AC group. With a median follow-up time of 24.4 months (interquartile range 17.9-24.4), the 2-year OS rate was 89.6% in the AC group and 81.8% in the CCRT group (P= 0.167). The 2-year DFS rate was 86.8% in the AC group and 74.6% in the CCRT group (P = 0.042). The 2-year LRFS rate was 91.5% in the AC group and 88.2% in the CCRT group (P = 0.443). The 2-year DMFS rate was 85.4% in the AC group and 79.6% in the CCRT group (P = 0.294). The most frequent serious (grade 3/4) nonhematologic toxicity was acute mucositis, which occurred 5% in the AC group vs 4% in the CCRT group (P = 0.498). For hematologic toxicity, grade 3-4 leukopenia were found 10% and 5% in the adjuvant and CCRT groups, respectively (P = 0.003). Multivariate analyses determined stage N2 disease was an adverse prognostic factor associated with shorter OS, DFS, and DMFS. And the adjuvant treatment was a significant protective factor for only DFS. CONCLUSIONS: The addition of adjuvant carboplatin/fluorouracil following CCRT with carboplatin significantly improved 2-year DFS in stage T2N0M0-T4N2M0 NPC albeit there was a nonsignificant trend in favor of a higher 2-year OS, LRFS, and DMFS. Long-term efficacy and late toxicities of AC still require exploration.

Arginine, glutamine, and fish oil supplementation in cancer patients treated with concurrent chemoradiotherapy: A randomized control study.

We evaluated the effectiveness of arginine, glutamine, and fish oil supplementation in patients' ability to adhere to the planned regimen and associated toxicities in patients who received concurrent chemoradiotherapy (CCRT). Eighty-eight cancer patients were randomized into 2 groups, A; regular diet and B; regular diet plus nutritional supplementation during their CCRT course. Logistic regression was used to assess the association between toxicity and the study groups. Survival analysis was performed using the Kaplan-Meier method, and log-rank tests were used to compare between the 2 groups. Among 88 patients, 45%, 32%, and 23% were head and neck cancer, esophageal cancer, and cervical cancer patients, respectively. Significantly higher grade 3-4 hematologic toxicities were found in group A than in group B (23% vs 5%, P= 0.03). The CCRT completion rate was lower in group A than in group B (75% vs 91%), but the difference was not statistically significant (P= 0.09). Adjusted for type of cancer and age, group B patients were associated with lower hematologic toxicities of CCRT, P= 0.03. Two-year overall survival was 47% for group A, and 61% for group B, P= 0.22. In conclusion, incidence of severe hematologic toxicities were significantly lower in patients with arginine, glutamine, and fish oil supplementation during CCRT. These findings, therefore, need further studies on the isocaloric design.

Iodine deficiency and thyroid cancer trends in three regions of Thailand, 1990-2009.

BACKGROUND: Iodine deficiency may play a role in thyroid cancer carcinogenesis. Because Thailand has region-specific historical iodine deficiency, it is ideal to evaluate the potential impact of recent national iodine supplementation policies on thyroid cancer incidence trends. METHODS: We examined thyroid cancer trends in Thailand from 1990 to 2009 in three geographically separated populations (Songkhla Province [south], Chiang Mai Province [north], and Khon Kaen Province [northeast]), each with a different historical prevalence of iodine deficiency. We used Joinpoint analysis and age-period-cohort (APC) models to investigate trends in thyroid cancer incidence. RESULTS: Pooled incidence of papillary cancers significantly increased (Males APC: 2.0, p<0.05; Females APC: 7.3 [1990-2001, p<0.05], -2.1 [2001-2009]) and incidence of follicular cancers significantly decreased (Males APC: -5.2, p<0.05; Females APC: -4.3 [1990-1998, p<0.05], 12.3 [1998-2001], -17.0 [2001-2005, p<0.05], 8.2 [2005-2009]) in both males and females between 1990 and 2009. The largest increases in papillary cancer incidence, and the largest decreases in follicular cancer incidence, occurred in historically iodine-deficient regions. Interestingly, the significant histological changes coincided with Thailand's most recent national iodination policy. The thyroid cancer trends in females were better explained by period effects than cohort effects. CONCLUSIONS: This study adds to the research indicating that papillary carcinoma incidence increases, and follicular carcinoma incidence decreases, as population-level iodine deficiency declines, and suggests that iodine exposure may affect late stages of thyroid carcinogenesis. However, our findings are limited by the ecological study design and lack of data prior to iodine supplementation.

Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: A literature review.

Toxicities resulting from platinum based chemotherapy in head and neck cancer is a cause for much concern. There is a lack of clinical criteria for defining these patient populations, which has posed serious problems associated with increased morbidity and consequently an adverse effect on patients' quality of life. In addition, there is a lack of consensus on clinical criteria for defining such patient populations, who may be unsuitable for concurrent chemoradiotherapy. A group of experts in the field of head and neck cancer from the Asia Pacific Region convened in August 2014 in Korea to discuss the development of a set of clinical criteria in order to fill the knowledge gap and provide a reference tool for head and neck oncologists. This paper reports the final output from this meeting and the accompanying literature review, with the aim of aiding clinical decision making with the help of some clinical criteria to identify platinum unsuitable patient populations in head and neck cancer management. Some alternative treatment options are also discussed in this paper.

Preoperative irinotecan/5-FU/leucovorin plus concurrent radiotherapy in rectal cancer.

PURPOSE: To evaluate results of preoperative irinotecan/5-FU/leucovorin plus radiotherapy for locally-advanced rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer were treated with preoperative irradiation 46 Gy plus concurrent chemotherapy(irinotecan 10 mg/m(2)/d d1-d5, d22-d26, 5-FU 350 mg/m(2)/d d1-d5, d22-d26, and leucovorin 20 mg/m(2) d1-d5, d22-d26), followed by radical surgery. RESULTS: There were no treatment-related deaths. Acute toxicity was mainly in neutropenia and diarrhea, with both grade 4 neutropenia and grade 3 diarrhea observed in 4 patients(11%). Radical resectability was performed in 29 patients(83%)with sphincter preservation surgery in 7 patients. Six patients did not undergo the planned surgery due to patient refusal and disease progression. A complete pathological response was observed in 14%(4/29). Pathological T-downstaging was observed in 55%(16/29). CONCLUSIONS: These results suggest that preoperative radiochemotherapy with irinotecan/5-FU/leucovorin is safe and effective in tumor downstaging and allows sphincter-saving resection to be performed in locally-advanced rectal cancer.

FOLFIRI chemotherapy for metastatic colorectal cancer patients.

OBJECTIVES: 1) To confirm the efficacy of irinotecan plus folinic acid/continuous 5-fluorouracil as bimonthly FOLFIRI regimen in metastatic colorectal cancer patients. Efficacy evaluations will include response rate, duration of response, and survival. 2) To evaluate safety profiles on patients receiving this combination. MATERIAL AND METHOD: Nineteen patients with metastatic colorectal cancer received 180 mg/m2 intravenous (iv) day 1 of irinotecan, 200 mg/m2 iv of folinic acid, 400 mg/m2 iv bolus days 1 to 2, 5-fluorouracil (5-FU), and 600 mg/m2 iv 5-FU infusion over 22 hours, days 1 to 2. Treatment was repeated every two weeks and one cycle contained three fortnightly administrations. Sites of disease were liver in nine patients, lungs in three patients, bowels in four patients, lymph nodes in three patients, and peritoneum in two patients. Two patients had > 1 metastatic site. Previous treatments included adjuvant chemotherapy in seven cases and front-line chemotherapy for advanced disease in one case. RESULTS: A median of six treatment cycles was completed (range, 2-13 cycles). All patients were assessable for toxicity and 16 patients were evaluable for treatment response. The non-hematological toxicity was mild. Most had grade 1 or 2. Only one patient experienced grade 3 fatigue and anorexia, and discontinued chemotherapy after the second cycle. There were no cases with grade 4 toxicity. Fourteen patients had at least grade 2 alopecia. The most common hematological toxicity was neutropenia. Grade 3 and 4 neutropenia were observed in three and two patients, respectively. There was no case of febrile neutropenia. Based on intention to treat analysis, there were no complete responses (CR), five (26.3%) partial response (PR), and 11 (57.9%) stable disease. With the median follow-up of 6.6 months, the median time to disease progression was 4.7 months and the median survival time was 10.6 months. CONCLUSION: Bimonthly irinotecan in combination with folinic acid and 5-fluorouracil was active with acceptable toxicities and a prolonged survival time in pretreated colorectal cancer. Additional trials to define the optimal dose and schedule of treatment are justified.

Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial.

PURPOSE: This is a prospective, Phase III multicenter randomized trial to assess the effectiveness of concurrent intravenous mitomycin C, oral 5-fluorouracil (5-FU), and radiotherapy (RT) in locally advanced carcinoma of the cervix. METHODS AND MATERIALS: Between January 1988 and November 1994, 926 patients with locally advanced carcinoma of the cervix, FIGO Stage IIB-IVA, were entered into this study. The patients were randomized into four arms, as follows: Arm 1: conventional RT; Arm 2: conventional RT and adjuvant chemotherapy; Arm 3: conventional RT plus concurrent chemotherapy; Arm 4: conventional RT plus concurrent chemotherapy and adjuvant chemotherapy. Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2) was given on Days 1 and 29, and oral 5-FU at 300 mg/day was administered on Days 1-14 and 29-42 during RT. Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks, with a 2-week rest every 6 weeks. Six centers participated in the trial. RESULTS: The median follow-up time was 89 months. Acute side effects were generally higher in concurrent arms, but most of the patients tolerated the treatment well. Bone marrow toxicity was also higher in concurrent arms. The 5-year actuarial disease-free survival (DFS) was 48.2%, 54.1%, 64.5%, and 59.7% for arms 1, 2, 3, and 4, respectively. The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm. The local recurrence was 25.5%, 20.6%, 14.3%, and 17.6% for arms 1, 2, 3, and 4, respectively. The metastatic rates were not significantly different in all four arms. At the time of analysis, there were no increases in late side effects, especially in gastrointestinal and genitourinary systems. CONCLUSIONS: Concurrent chemotherapy, mitomycin C, and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix.