[Supportive therapy and management of side effects in dermato-oncology]. / Supportivtherapie und Nebenwirkungsmanagement in der Dermatoonkologie.

In the context of supportive therapy, possible complaints which may be caused by the cancer itself, by the antitumoral therapy or by psychosocial concerns are considered. Due to the introduction of new anticancer drugs in dermato-oncology, clinicians are confronted with a novel spectrum of adverse events. There are a number of inflammatory, immune-mediated side effects caused by immunotherapies, which can affect virtually any organ. Targeted therapies also have specific side effects. Basically, the management of adverse events depends on their severity. Besides treatment breaks and dosage modifications, immunotherapy-related adverse events are treated with systemic immunosuppressants. Supportive symptomatic therapy is offered. The additional consideration of psychosocial problems can improve quality of life of cancer patients.

Quantitative survival impact of composite treatment delays in head and neck cancer.

BACKGROUND: Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC. METHODS: Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival. RESULTS: Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements. CONCLUSIONS: Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when considering survival burden. Cancer 2018. © 2018 American Cancer Society.

ED visits, hospital admissions and treatment breaks in head/neck cancer patients undergoing radiotherapy.

Objectives: Radiation therapy (RT) is an integral part of treatment of head/neck cancer (HNC) but is associated with many toxicities. We sought to evaluate sociodemographic, pathologic, and clinical factors associated with emergency department (ED) visits, hospital admissions (HA), and RT breaks in HNC patients undergoing curative-intent RT. Methods: We completed a Level 3 (Oxford criteria for evidence-based medicine) analysis of a cohort of HNC patients who underwent curative-intent RT at our institution from 2013 to 2017. We collected demographic characteristics and retrospectively assessed for heavy opioid use, ED visits or HA during RT as well as RT breaks. Treatment breaks were defined as total days to RT fractions ratio ≥1.6. Multivariable stepwise logistic regression analyses were done to determine the association of various sociodemographic, pathologic, and clinical characteristics with ED visits, HA and RT treatment breaks. Results: The cohort included 376 HNC patients (294 male, 82 female, median age 61). On multivariable analysis, significant factors associated with ED visits during RT were heavy opioid use and black race. Receipt of concomitant chemotherapy was the only factor associated with hospital admissions during RT. Advanced age, lower socioeconomic class, glandular site, and receipt of chemotherapy were all independently associated with RT breaks. Lower cancer stage and lack of substance abuse history were independently associated with lack of treatment breaks. Conclusion: HNC patients with factors such as heavy opioid use, Black race, receipt of concomitant chemotherapy, and lower socioeconomic class may require closer monitoring during RT.

Lower pretreatment hemoglobin status and treatment breaks in locally advanced head and neck squamous cell carcinoma during concurrent chemoradiation.

BACKGROUND: Treatment breaks during radiation for locally advanced Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the important factors affecting the loco-regional control rate. We prospectively analysed the role lower pre-treatment hemoglobin (pre-T Hb) status and its influence on treatment breaks amongst patients undergoing concurrent chemoradiation (CRT). METHODS: One hundred and twenty HNSCC (T3-T4a, N1-N2c) patients treated by CRT were prospectively analysed for influence of pre-T Hb on treatment breaks. Sub-sites included oral cavity, oropharynx, hypopharynx & larynx. All patients received radiation to a total dose of 66Gy to PTV along with weekly Inj. Cisplatin 40 mg/m2. All patients were evaluated weekly and at the end of 6 weeks by hemogram, physician and radiological examination. RESULTS: Our study population had a mean age (±standard deviation) of 55 (± 10.7) years (range: 27 - 69 years), 85 men and 35 women with a performance status of the Eastern Cooperative Oncology Group (ECOG) 1-2. The mean pre-T Hb calculated (using receiver operating characteristic curve [ROC]) was 10.3 g/dL. Among 120 patients, in the pre-T Hb of ≤10.3 g/dL group, 44 (75.9%) patients had treatment breaks of ≥5 days and 11 (17.7%) patients had treatment breaks < 5 days; in the pre-T Hb of >10.3 g/dL group, 14 (24.1%) patients had treatment breaks of ≥5 days and 51 (82.3%) patients had treatment breaks < 5 days (P = 0.001). CONCLUSION: Lower pre-T Hb level of ≤ 10.3 g/dL is statistically significantly associated with higher treatment breaks of ≥ 5 days.

Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis.

BACKGROUND: Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break. PATIENTS AND METHODS: An IPDMA of intermittent strategy impact on survival was undertaken, including all relevant trials in which data were available. Intermittent strategies were classified into two groups: a planned stopping of all therapy ("treatment break strategy"; 6 trials; 2,907 patients) or to the same treatment omitting oxaliplatin ("maintenance strategy"; 3 trials; 1,271 patients). The primary analysis sample was of patients successfully completing induction therapy. Additionally, a pre-planned analysis of the predictive value of thrombocytosis on survival under a continuous versus an intermittent strategy was undertaken. RESULTS: All trials had comparable inclusion criteria. The overall IPDMA of intermittent therapy versus continuous therapy demonstrated no detriment in OS (HR = 1.03 [95% CI 0.93-1.14]), whether from complete break (HR 1.04 [95% CI 0.87-1.26]) or maintenance strategies (HR 0.99 [95% CI 0.87-1.13]). Thrombocytosis was confirmed as a marker of poor prognosis in aCRC, but did not predict for OS detriment from treatment break strategies (interaction HR = 0.97 [95% CI 0.66-1.40] compared to continuous therapy). CONCLUSION: The highest levels of evidence from this IPDMA indicate no detriment in survival for patients receiving an intermittent therapy strategy, either for maintenance or complete break strategies. Although, thrombocytosis is confirmed as a marker of poor prognosis, it is not predictive of poor outcome for patients treated with intermittent therapy. An intermittent chemotherapy strategy can therefore be applied irrespective of baseline platelet count and does not result in inferior OS compared to continuous chemotherapy.

Effect of prophylactic granulocyte-colony stimulating factor (G-CSF) on acute hematological toxicity in medulloblastoma patients during craniospinal irradiation (CSI).

OBJECTIVES: Haematological toxicity and treatment breaks are common during cranio-spinal irradiation (CSI) due to irradiation of large volume of bone marrow. We conducted this study to see the effect of prophylactic granulocyte colony stimulating factor (GCSF) in reducing treatment breaks. PATIENTS AND METHODS: The study was conducted over a period of 15 months from August 2017 to November 2018. Histopathologically proven Medulloblastoma patients received prophylactic GCSF during CSI. Acute hematological toxicities and treatment breaks were noted and effect of age and pretreatment blood counts were analyzed by SPSS (Statistical Package for Social Sciences) version 23. RESULTS: A total of 28 patients were included in the study. During CSI, hematological toxicity leading to treatment breaks was observed in 11 (39.3 %) patients, of which grade 3 and 2 toxicities were seen in ten and one patients respectively. Younger age (<10 years) at diagnosis was significantly associated with the development of hematological toxicity (p = 0.028, Chi-Square). No correlation was found with pre-treatment blood counts. CONCLUSION: Prophylactic use of GCSF may be effective in preventing radiation induced hematological toxicity and treatment breaks.

Barriers affecting adherence to radiation treatment and strategies to overcome those barriers.

BACKGROUND: The WHO defines adherence as the extent to which a patient's behavior coincides with recommendations from a health-care provider. Nonadherence to cancer treatment has a major impact on the therapeutic outcome. AIM OF THE STUDY: To assess the prevalence of nonadherence to radiation regimen and to analyze the factors that affect adherence to cancer treatment. MATERIALS AND METHODS: Patients receiving radiation treatment in our hospital were screened for adherence to appointment keeping and to the prescribed radiation regimen and patients who had unplanned treatment breaks during treatment were interviewed. Between January and July 2013, we identified 61 patients who had unplanned breaks during treatment. We analyzed the social, emotional, educational, economic, and therapeutic barriers that led to nonadherence. RESULTS: Of the 61 patients who had unplanned breaks during treatment, 54% were males and 46% were females. Fifty-seven percent of patients had head and neck cancers and 25% had gynecological cancers. Seventy-one percent of patients were planned for concurrent chemoradiation. The number of days of unplanned treatment breaks ranged from 3 to 27 days. Social and therapeutic barriers were found to be the most common factor that led to nonadherence in these patients. CONCLUSION: Identification of barriers that lead to nonadherence, designing strategies to overcome such barriers and effective communication becomes imperative to ensure uninterrupted treatment. Based on the above analysis, we have designed several strategies to improve adherence to treatment among our patients.

Induction Chemotherapy and Sequential Concomitant Chemo-radiation in Locally Advanced Head and Neck Cancers: How Induction-phase Intensity and Treatment Breaks May Impact on Clinical Outcomes.

AIM: The purpose of the study was to assess outcomes of locally advanced head and neck (LAHNC) treated with induction chemotherapy (ICT) and subsequent concurrent chemo-radiation. PATIENTS AND METHODS: A total of 71 LAHNC patients were treated with 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy and subsequent concurrent chemoradiation with weekly cisplatin or carboplatin. Definitive radiotherapy was delivered with intensity-modulated radiation and a simultaneous integrated boost approach up to a total dose of 70 Gy in 35 fractions to the macroscopic primary and nodal disease. RESULTS: Actuarial 2-year OS, CSS, DFS, MFS, LC were 55.3% (95%CI=39.3-68.6), 58.6% (95%CI=41.9-72), 60.5% (95%CI=47.3-71.4), 87.3% (95%CI=76.2-93.5) and 74.7% (95%CI=61.5-83.9), respectively. On multivariate analysis undergoing to 3 vs. 2 cycles of TPF (HR=22.31; 95%CI=2.68-185.66; p=0.004) and radiotherapy treatment break >4 days (HR=1.28; 95%CI=1.06-1.55; p=0.01) negatively affected cancer-specific survival (CSS) with statistical significance. Achieving complete remission after ICT had a statistically significant impact on CSS (HR=0.9; 95%CI=0.01-0.54; p=0.009). Patients undergoing ICT with 3 cycles had more frequently treatment breaks compared to those submitted to 2 cycles (HR=1.36; 95%CI=1.06-1.73; p=0.01), and had statistically significant longer treatment break time (5.9+1.8 vs. 3+0.36; p=0.02). CONCLUSION: A shorter ICT phase may be a better option enhancing patients' tolerance during concurrent chemoradiation and affecting clinical outcomes.

Elimination of unplanned treatment breaks and dose reductions caused by mucositis: Positive implications for survival outcomes and cost reductions using high potency polymerized cross-linked sucralfate in 55 patients undergoing radiation for head and neck cancer with and without chemotherapy

PURPOSE: Annually 27,855 patients in Korea develop treatment-induced mucositis nearly doubling the cost of cancer care. It is an emergency medical condition causing unplanned treatment breaks in 4,998 patients. The subsequent reduction in optimal dose-intensity causes premature deaths due to lower 5-year survival. An additional 216 patients die from mucositis-mediated sepsis and infection. Thus complete elimination of mucositis will immediately reduce the cost of care while simultaneously eliminating 5,214 mucositis-associated deaths. High potency polymerized cross-linked sucralfate (HPPCLS) cleared by the US Food and Drug Administration has been associated with the elimination of mucositis.METHODS: Observational, self-reporting, practice-based mucositis registry. Inclusion criteria: any patient with chemoradiation-induced mucositis. Exclusion criteria: previous adverse reaction to sucralfate products. Primary outcome: rapid reversal or complete prevention. Conduct of study: 28 radiation oncologists from 21 different institutions prescribed HPPCLS to 55 patients undergoing chemoradiation for squamous cell carcinoma of head and neck and esophagus to eliminate mucositis-associated treatment breaks.RESULTS: All patients with World Health Organization grade 1 (n=6), grade 2 (n=23), grade 3 (n=16) oral mucositis, and grade 2 esophageal mucositis (n=2) experienced complete reversal of mucositis. Within 2–3 days both mucosa and swallowing normalized. Anticipated grade 3/4 mucositis was prevented in 8 out of 8 elderly patients aged 78–93 avoiding gastrostomy tube placement. Statistical analysis of outcomes: Outcomes qualified as a positive Glasziou treatment effect that was statistically significant (P<0.05).CONCLUSION: HPPCLS eliminated mucositis by rapid reversal or complete prevention, thereby eliminating unplanned treatment breaks. It may likely reduce mucositis-associated increased cost of care and premature deaths.

Balancing the efficacy and toxicity of chemotherapy in colorectal cancer.

As the therapeutic options for the treatment of colorectal cancer have expanded over the past 20 years, so has the complexity of decision making. The goals of treatment in the palliative, adjuvant and neoadjuvant settings vary and it is not only the efficacy of drugs that influence treatment decisions. Age, performance status, the presence of significant comorbidities and the different treatment regimens and strategies provide medical oncologists with an array of options to attempt to maximize patients' quality of life and longevity.