Impact of a mobile application (reminder app) on acute toxicity during radiotherapy of head-and-neck cancer - results of a randomized phase III trial (RAREST-02).

BACKGROUND: Radiotherapy of head-and-neck cancer (SCCHN) is often associated with acute toxicity. In a previous trial, daily reminders by staff members to perform skin care resulted in less dermatitis. This randomized trial investigated whether a mobile application can replace these reminders. METHODS: Patients were stratified according to tumor site, treatment and center. Fifty-three patients were eligible for per-protocol-set (25 with, 28 without app). Primary endpoint was grade ≥ 2 dermatitis until 60 Gy. Secondary endpoints included dermatitis grade ≥ 2 until end of radiotherapy (EOT), dermatitis grade ≥ 3, and mucositis grade ≥ 2 and ≥ 3. RESULTS: After an interim analysis, the study was terminated (delayed and slow accrual). Until 60 Gy, grade ≥ 2 dermatitis rates were 72% with vs. 82% without app (p = 0.38), grade ≥ 3 dermatitis rates 20% vs. 11% (p = 0.45). Until EOT, grade ≥ 2 and ≥ 3 dermatitis rates were 72% vs. 86% (p = 0.22) and 24% vs. 18% (p = 0.58). Until 60 Gy, grade ≥ 2 and ≥ 3 mucositis rates were 76% vs. 82% (p = 0.58) and 20% vs. 36% (p = 0.20). Until EOT, corresponding mucositis rates were 76% vs. 82% (p = 0.58) and 28% vs. 43% (p = 0.26). CONCLUSION: Given the limitations of this trial, the reminder app led to non-significant reduction of grade ≥ 2 dermatitis, grade ≥ 2 mucositis and ≥ 3 mucositis. Additional studies are required to define the value of reminder apps during radiotherapy for SCCHN.

Comparison of Two Cisplatin Regimens for Chemoradiation in Patients With Squamous-cell Carcinoma of the Head and Neck.

BACKGROUND/AIM: Many patients with squamous-cell carcinoma of the head and neck receive cisplatin-based chemoradiation. This retrospective study compared two chemoradiation programs to help identify the optimal cisplatin-regimen. PATIENTS AND METHODS: Forty-one patients assigned to chemoradiation with two cycles of 20 mg/m2/days(d)1-5 were compared to 78 patients assigned to chemoradiation with two cycles of 25 mg/m2/d1-4. Groups were compared for toxicity, loco-regional control (LRC), and survival. RESULTS: Both treatments were associated with similar rates of oral mucositis, radiation dermatitis, xerostomia, nausea, decreased renal function, and hematotoxicity. The cisplatin-regimen had no significant impact on LRC (p=0.41) or survival (p=0.85). Survival was significantly worse with radiotherapy interruptions (>1 week) or discontinuation (p<0.001) and administration of <80% of the planned cisplatin dose (p<0.001). CONCLUSION: Both cisplatin-regimens did not differ significantly regarding toxicities, LRC, and survival. It is important to avoid interruption or discontinuation of radiotherapy and to administer ≥80% of planned cisplatin.

A New Prognostic Instrument for Predicting the Probability of Completion of Cisplatin during Chemoradiation for Head and Neck Cancer.

Many head and neck cancer patients assigned to definitive or adjuvant chemoradiation treatment do not complete the concurrent cisplatin dose. We determined corresponding risk factors and developed a prognostic instrument to help identify these patients. Ten pre-treatment characteristics were retrospectively analyzed in 154 patients with head and neck cancer who were treated via chemoradiation with cisplatin. These pre-treatment characteristics included age, sex, Karnofsky performance score, tumor site, primary tumor stage, nodal stage, histologic grade, upfront surgery, human papilloma virus status, and history of smoking. The characteristics significantly associated with the completion of cisplatin-based treatment, the receipt of ≥80% cisplatin, or showing a strong trend of association after multivariate analyses were used for the prognostic instrument. For each characteristic, 0 points were assigned for worse outcomes, and 1 point was assigned for better outcomes. Patients' scores were calculated by adding these points. Age ≤ 60 years and a Karnofsky performance score of 90-100 were significantly associated with both endpoints after multivariate analysis, and male gender showed a trend for association with the receipt of ≥80% cisplatin. Patient scores were 0, 1, 2, and 3 points. The corresponding rates of completion of cisplatin-based treatment were 14%, 41%, 62%, and 72%, respectively (p = 0.004). The rates of receipt of ≥80% cisplatin were 29%, 54%, 72%, and 94%, respectively (p < 0.001). This new prognostic instrument helps to predict whether head and neck cancer patients scheduled for chemoradiation will receive cisplatin as planned.

First Results of Concurrent Chemoradiation with Two Courses of 5 × 25 mg/m2 Cisplatin for Locally Advanced Head and Neck Cancer.

Many patients with squamous cell carcinoma of the head and neck (SCCHN) receive cisplatin-based chemoradiation. Cisplatin 100 mg/m2 every three weeks is toxic and alternative cisplatin regimens are desired. Two courses of 20 mg/m2/day 1-5 (cumulative 200 mg/m2) were shown to be similarly effective and better tolerated than 100 mg/m2 every three weeks. Previous studies suggested that cumulative doses >200 mg/m2 may further improve outcomes. In this study, 10 patients (group A) receiving two courses of 25 mg/m2/day 1-5 (cumulative 250 mg/m2) in 2022 were retrospectively matched and compared to 98 patients (group B) receiving two courses of 20 mg/m2/day 1-5 or 25 mg/m2/day 1-4 (cumulative 200 mg/m2). Follow-up was limited to 12 months to avoid bias. Group A achieved non-significantly better 12-month loco-regional control (100% vs. 83%, p = 0.27) and metastases-free survival (100% vs. 88%, p = 0.38), and similar overall survival (89% vs. 88%, p = 0.90). No significant differences were found regarding toxicities, completion of chemotherapy, and interruption of radiotherapy. Given the limitations of this study, chemoradiation with two courses of 25 mg/m2/day 1-5 appears an option for carefully selected patients as a personalized treatment approach. Longer follow-up and a larger sample size are needed to properly define its role.

Emotional Distress in Head-and-neck Cancer Patients Scheduled for Chemoradiation or Radiotherapy Alone.

BACKGROUND/AIM: Radiotherapy for head-and-neck cancer is often associated with significant toxicities, which may cause emotional distress. We evaluated prevalence and risk factors for pre-treatment emotional problems in patients irradiated for head-and-neck cancer. PATIENTS AND METHODS: Twelve characteristics were retrospectively investigated in 213 patients for associations with emotional problems (worry, fear, sadness, depression, nervousness, loss of interest). After Bonferroni adjustment, p-values <0.0042 were regarded significant. RESULTS: At least one emotional problem was reported by 131 patients (61.5%). Specific prevalence for emotional problems ranged between 10% and 44%. Physical complaints showed significant associations with all six emotional problems (p<0.0001) and female sex with sadness (p=0.0013). Trends were found for associations between female sex and fear (p=0.0097), history of another tumor and sadness (p=0.043), worse performance status and nervousness (p=0.012), and cancer site (oropharynx/oral cavity) and nervousness (p=0.063). CONCLUSION: More than 60% of patients reported emotional distress prior to radiotherapy for head-and-neck cancer. Patients with risk factors likely require near-term psycho-oncological assistance.

Chemoradiation with Cisplatin vs. Carboplatin for Squamous Cell Carcinoma of the Head and Neck (SCCHN).

Cisplatin is the standard for the chemoradiation of squamous cell carcinoma of the head and neck (HNSCC). Many patients cannot receive cisplatin due to impaired renal function. This study investigated carboplatin as an alternative option. In total, 131 patients assigned to two courses of cisplatin (20 mg/m2/d1--5 or 25 mg/m2/d1-4) were matched to 45 patients not suitable for cisplatin and receiving carboplatin (AUC 1.0/d1-5 or AUC 1.5/d1-4). The endpoints included loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS), toxicities, and the completion of chemotherapy. The patients in the carboplatin group were significantly older and had more G3 tumors. Otherwise, the baseline characteristics were balanced. The LRC rates at 2 and 3 years were 77% and 76% in the cisplatin group vs. 69% and 65% in the carboplatin group (p = 0.21). The MFS rates were 83% and 78% vs. 78% and 74% (p = 0.34) and the OS rates 83% and 79% vs. 83% and 75% (p = 0.64), respectively. The outcomes were not significantly different in the subgroups receiving definitive or adjuvant chemoradiation. No significant differences were found regarding toxicities. Non-significantly more patients in the carboplatin group completed their chemotherapy (78% vs. 66%, p = 0.15). Carboplatin was associated with similar outcomes and toxicities as cisplatin, although these patients had worse renal function, more aggressive tumors, and were older. Given the limitations of this study, carboplatin appears an option for patients not suitable for cisplatin.

The First Prognostic Tool to Estimate the Risk of Late Grade ≥3 Xerostomia in Patients Irradiated for Head-and-Neck Cancer.

BACKGROUND/AIM: Xerostomia is a serious complication following radiotherapy of head-and-neck cancers. A prognostic tool was developed for estimating its risk. PATIENTS AND METHODS: In our previous study, age, tumor site, bilateral lymph node involvement, definitive radiotherapy, and addition of systemic therapies showed significant associations with grade ≥3 late xerostomia or trends. In additional analyses, mean radiation dose to ipsilateral parotid gland was significant (p=0.011). These six factors were included in the prognostic tool. Scoring points of 0 (lower risk) or 1 (higher risk) were assigned to each factor and added for each patient. RESULTS: Patient scores ranged between 0 and 6; Grade ≥3 xerostomia rates were 0%, 8%, 24%, 26%, 25%, 42%, and 100%, respectively. Three groups were designed (0-1, 2-4, and 5-6 points) with grade ≥3 xerostomia rates of 5%, 25%, and 50%, respectively (p<0.001). CONCLUSION: This new tool helps estimating the risk of radiation-induced grade ≥3 xerostomia. It can support physicians and other medical staff members during treatment planning.

Risk Factors for Xerostomia Following Radiotherapy of Head-and-Neck Cancers.

BACKGROUND/AIM: Many head-and-neck cancer patients receive radiotherapy, which may be associated with significant toxicities. Xerostomia is considered one of the most debilitating late adverse events. This study was performed to identify risk factors for xerostomia. PATIENTS AND METHODS: Several characteristics were investigated for associations with late xerostomia in 159 patients irradiated for head-and-neck cancer including age, sex, tumor site and size, underlying pathology, histologic grading, upfront resection, systemic treatment, and type and dose of radiotherapy. RESULTS: Ninety (57%) and 35 (22%) patients experienced grade ≥2 and ≥3 xerostomia, respectively. Grade ≥2 xerostomia was significantly associated with tumor site (nasopharynx/oropharynx/oral cavity/floor of mouth, p=0.049). Grade ≥3 xerostomia was significantly associated with age ≥61 years (p=0.035); trends were found for tumor site (p=0.088), bilateral nodal involvement (p=0.093), definitive treatment (p=0.082), and systemic treatment (p=0.055). CONCLUSION: Risk factors for xerostomia following radiotherapy of head-and-neck cancers were identified including older age, unfavorable tumor site, bilateral involvement of lymph nodes, definitive treatment, and addition of systemic therapies. For patients with risk factors, sparing of the salivary glands is particularly important.

Impact of Dose-Volume Parameters of Parotid Glands on Xerostomia in Patients Irradiated for Head-and-Neck Cancer.

BACKGROUND/AIM: Optimal planning of radiotherapy for head-and-neck cancers should consider the risk of xerostomia. This study investigated the prognostic value of dosevolume parameters of the parotid glands. PATIENTS AND METHODS: Dose-volume parameters were evaluated for xerostomia in 145 patients including D40 (minimum dose to 40% of corresponding parotid volume), D60 (minimum dose to 60%), D80 (minimum dose to 80%), and mean dose of ipsilateral, contralateral, and bilateral parotid glands. RESULTS: Grade ≥2 xerostomia was significantly associated with D40 of ipsilateral and all parameters of bilateral glands; trends were found for all other parameters. Grade ≥3 xerostomia was significantly associated with D80 of bilateral glands; trends were found for other parameters of ipsilateral and bilateral glands. CONCLUSION: Since grade ≥2 xerostomia was associated with all parameters, D40, D60, and D80 did not provide additional information to mean doses. D80 of bilateral glands is a new factor and more predictive than mean dose regarding grade ≥3 xerostomia.

Prognostic Factors for Complete Recovery From Xerostomia After Radiotherapy of Head-and-Neck Cancers.

BACKGROUND/AIM: Radiotherapy of head-and-neck cancers can cause xerostomia. This study investigated potential prognostic factors for complete recovery from this complication. PATIENTS AND METHODS: Eighty head-and-neck cancer patients with radiation-induced xerostomia were retrospectively evaluated. Thirteen characteristics were analyzed for complete recovery (to grade 0) from xerostomia including age, sex, tumor site and stage, nodal stage, upfront surgery, mean dose to ipsilateral, contralateral and both parotid glands, chemotherapy, radiation type and dose, and initial grade of xerostomia. RESULTS: Fifteen patients (18.8%) experienced complete recovery of xerostomia. Significant associations with complete recovery were found for initial grade 1 xerostomia (p<0.001), mean dose to contralateral parotid gland of <20 Gy (p=0.034), and radiation treatment without chemotherapy (p=0.047). CONCLUSION: Almost every fifth patient experienced complete recovery of xerostomia. Prognostic factors were identified that can guide radiation oncologists during the process of treatment planning.

Accelerated Fractionation With Concomitant Boost vs. Conventional Radio-chemotherapy for Definitive Treatment of Locally Advanced Squamous Cell Carcinoma of the Head-and-Neck (SCCHN).

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.

A New Survival Score for Patients Scheduled for Palliative Irradiation of Locally Advanced Carcinoma of the Head-and-Neck.

BACKGROUND/AIM: Patients with advanced squamous cell carcinoma of the head-and-neck (SCCHN) may be assigned to palliative irradiation. A survival score was developed for this group to support treatment personalization. PATIENTS AND METHODS: Seventy-eight patients who received palliative irradiation for SCCHN and had complete data regarding performance score, pre-radiotherapy hemoglobin levels, and main tumor site were included in this retrospective study. Six-month survival rates of these factors were divided by 10 (factor scores) and added for each patient (total patient scores). RESULTS: Total patient scores ranged between 8 and 15 points. Three groups were designed based on the 6-month survival rates, namely 8-9 (n=15), 11-13 (n=36), and 14-15 (n=27) points. Six-month survival rates were 13%, 28%, and 63%, and median survival times were 1, 2, and 11 months (p=0.001). CONCLUSION: A new survival score including three prognostic groups was developed. This new tool can help physicians when designing personalized treatments for patients with SCCHN scheduled for palliative irradiation.

Palliative Local Radiotherapy for Advanced Squamous Cell Carcinoma of the Head-and-Neck: Prognostic Factors of Survival.

BACKGROUND/AIM: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients. PATIENTS AND METHODS: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed. Fourteen characteristics were evaluated for survival including age, gender, performance score, pre-radiotherapy hemoglobin, tumor site and stage, histologic grade, p16-status, equivalent dose in 2 Gy-fractions (EQD2), completion of radiotherapy, upfront surgery and systemic therapy. RESULTS: On univariate analysis, improved survival was significantly associated with pre-radiotherapy hemoglobin ≥12 g/dl (p=0.003), EQD2 >42.3 Gy (p=0.003) and completion of radiotherapy (p<0.001). In the multivariate analysis, hemoglobin levels remained significant (p=0.024). Trends were found for EQD2 (p=0.057) and completion of radiotherapy (p=0.093). CONCLUSION: Prognostic factors for survival were identified that can facilitate treatment personalization. The fact that higher EQD2 and completion of radiotherapy were associated with improved survival demonstrates the importance of close monitoring and care of these patients during radiotherapy.

Accelerated Fractionation Plus Chemotherapy Versus Conventionally Fractionated Radiochemotherapy for Unresectable Head-and-Neck Cancer.

BACKGROUND/AIM: Prognosis of patients with unresectable squamous cell carcinomas of the head and neck requires improvement. This retrospective study compared accelerated radiotherapy plus chemotherapy to conventional radiochemotherapy. PATIENTS AND METHODS: Patients received definitive treatment with accelerated radiotherapy plus chemotherapy (group A, n=10) or conventional cisplatin-based radiochemotherapy (group B, n=85). Groups were matched for several patient and tumor characteristics and compared for locoregional control (LRC), overall survival (OS) and toxicities. Additionally, accelerated radiotherapy plus chemotherapy and chemotherapy regimens in group B were compared for LRC and OS. RESULTS: Treatment type had no significant impact on LRC (p=0.98) and OS (p=0.57). In group A, toxicities occurred more often, including grade ≥3 mucositis (p=0.041), grade ≥2 lymphedema (p=0.007) and grade ≥3 leucopenia (p=0.007). Best 2-year LRC (p=0.39) and OS (p=0.015) was achieved with 20 mg/m2 cisplatin days 1-5 every 4 weeks; accelerated radiochemotherapy resulted in second-worst outcomes. CONCLUSION: Given the limitations of this study, accelerated radiotherapy plus chemotherapy provided no significant benefit but increased toxicity compared to conventional radiochemotherapy.