Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action.

PURPOSE: Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based. METHODS: We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor. RESULTS: The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk. CONCLUSION: Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised.

A mixed-methods study to explore the supportive care needs of breast cancer survivors.

OBJECTIVE: Needs assessment is the essence of quality cancer survivorship care. The aim of this study was to explore the supportive care needs of breast cancer survivors (BCS) in the first 5 years post treatment. METHODS: A mixed-methods approach was employed. A quantitative study included a Supportive Care Needs Survey, which was completed by 250 BCS to identify the level of their needs for help. The quantitative data informed semistructured qualitative interviews undertaken with 60 BCS to explore in detail their posttreatment needs and experiences. RESULTS: 32.4% and 16.8% reported 1 to 5 and greater than or equal to 6 needs for help, respectively. The regression analyses revealed that women within 2 years posttreatment and with higher educational level had higher levels of Psychological and Health Care System/Information needs. The qualitative data revealed "continuity of care" and "lifestyle advice and self-management" as prominent survivorship concerns. It was shown that determination to continue normal life, social support, and feeling overwhelmed by information were all experienced as important influences on survivors' need for help. CONCLUSIONS: Posttreatment needs vary with BCS characteristics and to the domains concerned. The approach to posttreatment care needs to be personalized and viable.

Unmet needs mediate the relationship between symptoms and quality of life in breast cancer survivors.

PURPOSE: This study aimed to compare the symptoms, unmet needs, and QoL reported by women at 6 months to <2 years and 2 to 5 years following surgery and adjuvant treatment for breast cancer. It also evaluated the relationships among symptoms, unmet needs, and QoL using structural equation modeling. METHODS: In this study, 113 and 137 survivors following breast cancer treatment 6 months to <2 years and 2 to 5 years, respectively, completed the Memorial Symptom Assessment Scale, the Supportive Care Needs Survey-34, and the Medical Outcomes Study 12-item Short Form Health Survey version 2.0 during their medical follow-up. RESULTS: The mean numbers of symptoms and unmet needs were 5.43 and 3.0, respectively, for survivors at <2 years, and 5.24 and 2.42, respectively, for survivors at 2 to 5 years following treatment. The most common reported symptoms were related primarily to physical domains. No significant differences were found between the two survivor groups on the MSAS scores. Survivors at <2 years reported significantly higher scores in Psychological and Health Care System/Information needs (p < 0.01), and lower composite scores in physical and mental QoL (p < 0.05) than those at 2 to 5 years post-treatment. Significant direct and indirect effects were found of symptom burden through unmet needs on survivors' physical and mental QoL after adjustment for survival time, and the models showed a good fit. CONCLUSIONS: Results suggest that breast cancer survivors continue to endure many symptoms independent of the survivorship period. The unmet needs mediate the relationship between symptom burden and survivors' QoL.

Perceived symptoms and the supportive care needs of breast cancer survivors six months to five years post-treatment period.

PURPOSE: This study characterized the range and levels of perceived symptoms and unmet needs reported by breast cancer survivors in the half-year to five year post-treatment period, and determined whether the symptoms can be a predictor of unmet needs. METHODS: In a cross-sectional study, 150 breast cancer survivors (mean age: 55.1 ± 8 years) at the half-year to five year post-treatment period were enrolled for analysis. The measuring scales used included the Memorial Symptom Assessment Scale (MSAS), and the Supportive Care Needs Survey Short Form (SCNS-SF34). RESULTS: 88% of the survivors reported having at least one symptom, while 51% reported at least one unmet need. Lack of energy was the most prevalent symptom (47%), followed by numbness/tingling in hands/feet (41%). Most of the survivors had unmet needs in the Health care system/Information domain (37% reported at least one unmet need for help), followed by Psychological needs (29%). The mean scores for the SCNS-SF34 domains, except for sexuality, were significantly higher in the high-symptom group (mean 17.6-32.2) compared with the low-symptom group (mean 3.5-22.3) (p < 0.01). Regression of the SCNS-SF34 domain scores against the MSAS scores revealed an increase in the explained variance of from 14% to 54%. CONCLUSION: Our results suggest that breast cancer survivors continue to experience a multitude of symptoms, and the burden of symptoms may be associated with unmet needs across a range of domains.

Psychometric properties of the Chinese version of Sexual Function After Gynecologic Illness Scale (SFAGIS).

PURPOSE: This study aims to develop the Chinese version of the Sexual Function after Gynecologic Illness Scale (SFAGIS) and to establish its psychometric properties in Hong Kong Chinese patients with gynecological cancer. METHODS: A Chinese version of SFAGIS was developed using the Brislin model of translation and guidelines for cross-cultural adaptation of scales. The content validity and semantic equivalence were assessed by an expert panel. The translated version of SFAGIS was administered to 150 Hong Kong Chinese women with gynecological cancer to test the scale's psychometric properties and to assess its feasibility. The convergent validity of the Chinese scale was tested by correlating it with the Chinese version of the sex relations subscale of the Psychosocial Adjustment to Illness Scale Self-Report (PAIS-SR). RESULTS: The average completion time for the Chinese SFAGIS was 16.2 ± 6.6 min. The internal consistency of the Chinese SFAGIS was 0.93. Test-retest reliability was also high with an interclass correlation coefficient 0.76. A Pearson product-moment correlation found strong correlations among the Chinese SFAGIS and the Chinese version of the sex relations subscale of the PAIS-SR, indicating that both scales measure the same as or has a similar construct. CONCLUSIONS: The Chinese version of SFAGIS is a reliable and valid instrument which can be used in clinical practice and research for assessing sexual function problems in Chinese patients with gynecological cancer and to identify those in need of attention.

Impact of mood disturbance, sleep disturbance, fatigue and pain among patients receiving cancer therapy.

This paper describes the prevalence of mood disturbance, sleep disturbance, fatigue and pain (MSFP), either alone or in combination in patients receiving cancer therapy, and determines its impact and whether it is a predictor for functional status and the impairment of quality of life (QoL). This is a cross-sectional study using secondary data from a sample of 214 patients being treated by chemotherapy or radiotherapy. In all, 87%, 68%, 66% and 38% of the patients reported MSFP respectively. Co-occurrence of any three and all of the four symptoms, were reported separately at rates of 29% and 31%. Patients with all four symptoms recorded significantly lower Karnofsky Performance Scale (KPS) scores (mean 77.7 ± 12.9) and QoL scores (mean subscales scores 9.0-17.6) than those with none or up to any three of the symptoms (P < 0.001). Regression of the KPS and QoL scores against the MSFP revealed an increase in the explained variance of 25%, 43%, 27%, 37% and 41% respectively for KPS, physical, emotional, functional and total QoL. The results suggest that MSFP are highly prevalent, whether alone or in combination, in patients receiving cancer therapy, and may negatively influence the patient's functional status and QoL during cancer therapy.

Colorectal cancer screening behaviour and associated factors among Chinese aged 50 and above in Hong Kong - a population-based survey.

PURPOSE: This study reports the uptake rate of colorectal cancer screening among Chinese people aged 50 or above and the identified factors associated with the likelihood of undergoing such screening. METHODS: A cross-sectional population-based telephone survey was conducted in Hong Kong during the period 2 to 28 May 2007. The survey covered demographics, perceived health status and susceptibility to cancer, utilisation of complementary medicine, family history of cancer and cancer screening behaviour. RESULTS: The survey was completed by 2004 Hong Kong Chinese residents aged 50 or older (response rate = 66.6%). The uptake rate of a fecal occult blood test and a colonoscopy was 12% and 19% respectively. Factors associated with colorectal cancer screening behaviour included: male participants, ex-smokers, with cancer or other serious disease, a family history of cancer, perceived health status fair or poor, regular visits to a doctor to look after health, and utilisation of complementary medicine. CONCLUSIONS: The uptake rate of this study population was low though an increasing trend did appear. Heath education and promotion programmes may focus on these identified factors to facilitate colorectal cancer screening in a Chinese population.

A systematic review of the effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients.

The aim of this systematic review was to assess the effectiveness of Chinese medicinal herbs used concurrently with cancer treatments in terms primarily of toxicity management but also quality of life and survival in adult cancer patients. Forty-nine trials met the inclusion criteria and were reviewed according to standard processes of systematic reviews. These trials included 3992 patients. All studies with the exception of one were of low methodological quality. The vast majority of the studies have shown that Chinese medicinal herbs improved treatment side effects, quality of life, and performance status, and some have provided evidence of tumour regression and increased survival. While no clinical recommendations can derive from such low quality studies, the number of studies reporting positive results is high enough to suggest that Chinese medicinal herbs may have a role in cancer care. However, more methodologically rigorous studies need to be developed as a priority before any firm conclusions can be drawn.

Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea/vomiting and oral mucositis in children with cancer.

Oral mucositis is a major toxicity associated with high-dose methotrexate (HD-MTX) therapy in the treatment of children with acute lymphoblastic leukaemia and osteosarcoma. This pilot matched case-control study investigated the associations between plasma concentration of MTX at 42 (p-MTX(42h)) and 66 (p-MTX(66h)) h, absolute neutrophil count (ANC) < or = or >1.0 x 10(9)/l, serum transaminases (ASAT/ALAT) < or > or =58 U/l, WHO < or > or =grade 2 nausea/vomiting and WHO < or > or =grade 2 oral mucositis. In this study, 11 children with WHO > or =grade 2 oral mucositis were compared with 17 control children matched for age, diagnosis and MTX-dosage. The results indicated that children with p-MTX(42h) > or = 1.0 micromol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p-MTX(42h) < 1.0 micromol/l. Children with p-MTX(66h) >= 0.2 micromol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p-MTX(66h) < 0.2 micromol/l. Children with ANC < or = 1.0 x 10(9)/l had an OR of 1.2 of developing oral mucositis when compared with the referent group of children who had ANC > 1.0 x 10(9)/l. In comparison with the referent group of children, who had <58 U/l ASAT/ALAT, those with ASAT/ALAT > or = 58 U/l had an OR of 1.2 of developing oral mucositis. Finally, children with WHO grade > or =2 nausea/vomiting had an elevated risk of developing oral mucositis when compared with the referent group of children who had WHO grade <2 nausea/vomiting (OR = 8.7). In conclusion, the results in this preliminary study provide support for the hypothesis that the risk of oral mucositis is associated with the plasma MTX concentration at 66 h and the level of nausea/vomiting.

Children's acceptance and tolerance of chlorhexidine and benzydamine oral rinses in the treatment of chemotherapy-induced oropharyngeal mucositis.

Oral care is of great importance in the prevention of chemotherapy-induced oropharyngeal mucositis. Although considerable attention has been given in improving oral care practices, patients' acceptance and tolerance of oral rinses is a continuing problem in oral care. A randomized crossover design was used to determine the relative acceptability and tolerability of chlorhexidine and benzydamine oral rinse agents in children receiving chemotherapy. At the end of the study, each subject was asked to compare these two agents in relation to stinging and taste, as well as his/her perception in reducing mucositis. Thirty-four children aged 6-17 years completed two courses of chemotherapy during which they alternately practiced oral care using chlorhexidine then benzydamine or benzydamine then chlorhexidine. All of the children tolerated the agents well and continued with rinsing throughout the study. Only a few children had to resort to diluting the agents with normal saline or water. Fifty-nine percent of children reported that the stinging associated with benzydamine was more accepted than chlorhexidine. The taste of both these agents was accepted by 50% of children. Approximately 60% of children reported that chlorhexidine was more helpful than benzydamine in reducing mucositis. About 47% and 50% of them preferred chlorhexidine and benzydamine in their subsequent chemotherapy, respectively. In conclusion, chlorhexidine and benzydamine are acceptable and well-tolerated by children over the age 6 years old.

Prevention of oral mucositis in paediatric patients treated with chemotherapy; a randomised crossover trial comparing two protocols of oral care.

This study compared the efficacy of two protocols for oral care using either chlorhexidine or benzydamine as oral rinses to alleviate mucositis in children undergoing chemotherapy. Eligible participants were randomised to receive either protocol for 3 weeks in a two-period crossover design. The occurrence of ulcerative lesions and severity of mucositis were measured at baseline and twice weekly, using the modified Oral Assessment Guide (OAG). Data were continuously analysed by plotting them directly on predefined sequential charts. According to this sequential analysis, the study could be terminated at the 34th within subject comparison, with a statistically significant reduction in ulcerative lesions (P<0.05) and severity of mucositis (P<0.05) in children on the chlorhexidine protocol. These findings suggest that chlorhexidine together with oral care might be helpful in alleviating mucositis when given prophylactically to children on chemotherapy, but the therapeutic benefit needs to be confirmed in a larger trial.

Palliation of oral mucositis symptoms in pediatric patients treated with cancer chemotherapy.

This prospective randomized 2-period crossover study aimed at comparing the efficacy of 2 oral care protocols differing in the type of mouthwashes: chlorhexidine versus benzydamine in alleviating oral mucositis symptoms for children undergoing chemotherapy. Forty subjects were randomly allocated to receive either chlorhexidine first then benzydamine protocols or benzydamine first then chlorhexidine protocols. Each protocol was started on the first day of chemotherapy and continued for 21 days. Subjects were evaluated in intervals of 3 to 4 days using the World Health Organization (WHO) grading for mucositis and 10-cm visual analogue scale for oral symptoms evaluations. Among 34 evaluable subjects, 26% and 48% of them using chlorhexidine and benzydamine had WHO grade II mucositis, respectively (P < .05). The results revealed a significant difference in mean area under the curve (AUC) of mouth pain (1.35 +/- 2.26 versus 3.09 +/- 3.21) (P = .05), and a trend of a lessening of mean AUC of difficulty in eating/chewing (2.49 +/- 3.74 versus 2.71 +/- 4.1) (P = .82) and swallowing (1.34 +/- 3.31 versus 1.91 +/- 4.03) (P = .53) for subjects receiving chlorhexidine compared to those receiving benzydamine. In conclusion, chlorhexidine may be helpful in palliating mucositis symptoms for children in chemotherapy. The beneficial effect, however, is small and needs to be confirmed in a larger trial.

An oral care protocol intervention to prevent chemotherapy-induced oral mucositis in paediatric cancer patients: a pilot study.

The likelihood of paediatric cancer patients experiencing oral mucositis has increased significantly as high-dose and multiple chemotherapy agents are used in the treatment of childhood cancer in recent years. The resulting oral ulcerative lesions can cause significant pain, dysphagia, alteration in nutritional status and increased risk for localized infections that could disseminate systemically. The purpose of this pilot study was to determine the clinical benefits of an oral care protocol intervention on the prevention and reduction of the severity of oral mucositis in paediatric patients receiving chemotherapy. Fourteen children were enrolled in the study; there were seven children in the control and seven in the experimental group. In the experimental group, children received a preventive oral care protocol consisting of tooth brushing, normal saline rinse and 0.2% chlorhexidine mouth rinse. Children in the control group received usual care according to the study's clinical setting. Data were collected at baseline, then twice a week for 3 weeks. The incidence of ulcerative lesions, severity of oral mucositis and the related pain intensity were used as the main outcome variables. The experimental group exhibited fewer and less painful oral mucositis lesions. The results of this study support the preventive use of oral care protocols in paediatric patients undergoing chemotherapy for cancer treatment.