Setup margins based on the inter- and intrafractional setup error of left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT).

PURPOSE: The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. METHODS: The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV-CBCT. Three hundred and three radiotherapy fractions of 23 left-sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre-treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. RESULTS: The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter- and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. CONCLUSION: With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left-sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV-CBCTs, thereby saving treatment time and radiation exposure.

Long-term effect and prognostic factors of a low-dose radiotherapy of painful plantar calcaneal spurs : A retrospective unicenter study.

PURPOSE: To estimate the long-term effect of low-dose radiotherapy of painful plantar calcaneal spurs, and to verify possible prognostic factors. PATIENTS AND METHODS: In this retrospective unicenter study, electronic patient files of patients with painful plantar calcaneal spurs treated with low-dose radiotherapy between July 2009 and February 2020 were reviewed. The low-dose radiotherapy consisted of a total dose of 3.0 Gy given with a fraction dose of 0.5 Gy three times a week. The pain reduction was estimated using a patient questionnaire with a visual analogue scale. Kaplan-Meier statistics and Cox regression analysis were used for the statistical analysis. RESULTS: Altogether, 864 heels of 666 patients were reviewed. The probability of an insufficient pain control 10 years after low-dose radiotherapy was 45.9% (95% confidence interval 39.4-52.4%) in the subset of patients with a minimum follow-up of 3 months (582 heels of 467 patients). Patients with an unsatisfactory pain reduction 3 months after low-dose radiotherapy were offered a re-irradiation. Forty percent of the patients who received a re-irradiation developed good pain reduction. Occurrence of an initial aggravation of pain during or within 3 months after low-dose radiotherapy (p = 0.005), and treatment of bilateral painful plantar calcaneal spurs (p = 0.008) were identified as significant unfavorable prognostic factors on univariate analysis. On multivariate analysis, the initial aggravation of pain remained as independent significant prognostic factor (p = 0.01). No clear radiation toxicity was observed. CONCLUSIONS: Low-dose radiotherapy is a safe and effective treatment option for patients with painful plantar calcaneal spurs. An initial aggravation of pain during or within 3 months after radiotherapy was identified as unfavorable prognostic factor for the treatment outcome. Re-irradiation of patients with an unsatisfactory pain reduction after low-dose radiotherapy is effective and should be offered to patients.

Better compliance with hypofractionation vs. conventional fractionation in adjuvant breast cancer radiotherapy : Results of a single, institutional, retrospective study.

BACKGROUND: The aim of the study was to identify factors significantly associated with the occurrence of unintended treatment interruptions in adjuvant breast cancer radiotherapy. PATIENTS AND METHODS: Patients treated with postoperative radiotherapy of the breast or chest wall between March 2014 and August 2016 were evaluated. The radiotherapy regimens and techniques applied were either conventional fractionation (CF; 28 daily fractions of 1.8 Gy or 25 fractions of 2.0 Gy) or hypofractionation (HF; 15 daily fractions of 2.67 Gy) with inverse planned intensity-modulated radiotherapy (IMRT) or three-dimensional planned conformal radiotherapy (3DCRT). Logistic regression analysis was used to identify factors associated with noncompliance. Noncompliance was defined as the missing of at least one scheduled radiotherapy fraction. RESULTS: In all, 19 of 140 (13.6%) patients treated with HF and 39 of 146 (26.7%) treated with CF experienced treatment interruptions. Of 23 factors tested, the fractionation regimen emerged as the only independent significant prognostic factor for noncompliance on multivariate analysis (CF; p = 0.007; odds ratio, 2.3; 95% confidence interval, 1.3-4.2). No statistically significant differences concerning the reasons for treatment interruptions could be detected between patients treated with CF or HF. CONCLUSION: HF is significantly associated with a better patient compliance with the prescribed radiotherapy schedule compared with CF. The data suggest that this finding is basically related to the shorter overall treatment time of HF.

Image-guided intensity-modulated radiotherapy of prostate cancer: Analysis of interfractional errors and acute toxicity.

PURPOSE: The aim of the study was to estimate interfractional deviations in patient and prostate position, the impact of the frequency of online verification on the treatment margins, and to assess acute radiation reactions of high-dose external beam image-guided intensity-modulated radiotherapy (IG-IMRT) of localized prostate cancer. PATIENTS AND METHODS: IG-IMRT was performed by daily online verification of implanted fiducial prostate markers using a megavoltage electronic portal imaging device (EPID). A total of 1011 image-guided treatment fractions from 23 consecutive unselected prostate cancer patients were analyzed. The median total dose was 79.2 Gy (range 77.4-81.0 Gy). Acute radiation reactions were assessed weekly during radiotherapy using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. RESULTS: A relevant combined patient set-up and prostate motion population random error of 4-5 mm was observed. Compared to daily IGRT, image guidance every other day required an expansion of the CTV-PTV (clinical target volume-planning target volume) margin of 8.1, 6.6, and 4.1 mm in the longitudinal, vertical, and lateral directions, thereby, increasing the PTV by approximately 30-40 %. No grade 3 or 4 acute radiation reactions were observed with daily IG-IMRT. CONCLUSION: A high dose with surprisingly low acute toxicity can be applied with daily IG-IMRT using implanted fiducial prostate markers. Daily image guidance is clearly superior to image guidance every other fraction concerning adequate target coverage with minimal margins.

A scoring system for predicting the survival prognosis of patients receiving stereotactic body radiation therapy (SBRT) for 1-3 lung metastases.

INTRODUCTION: The main goal of the present study was the development of a survival scoring system for patients treated with stereotactic body radiation therapy (SBRT) for very few lung metastases. Such an instrument would be of value when selecting the optimal dose for individual patients with a limited number of pulmonary lesions. METHODS: Forty-six patients receiving SBRT for 1-3 lung metastases were retrospectively analyzed. The biologically effective dose plus nine characteristics [gender, age, performance score, interval from tumor diagnosis to SBRT, primary tumor type, additional (extra-pulmonary) metastases, major location of lung metastases, number of pulmonary lesions, and volume treated with SBRT] were evaluated. Characteristics significantly associated with the survival on Cox regression analysis were incorporated in the scoring system. Scoring points were received from 1-year survival rates divided by 10. Sums of these scoring points represented the scores for the individual patients. RESULTS: Survival rates at 1 and 2 years were 66 and 56 %, respectively. On Cox regression analysis, performance score (p = 0.025), the type of primary tumor (p = 0.013) and the additional metastases (p = 0.032) had a significant impact on survival. Scores for patients ranged from 15 to 25 points. Three groups were designed: 15 points, 16-20 points, and 21-25 points. One-year survival rates were 0, 52, and 83 %, respectively (p = 0.005); 2-year survival rates were 0, 52, and 66 %, respectively. CONCLUSION: A survival scoring system for patients receiving SBRT for very few lung metastases was developed. This score allowed us to estimate the survival prognosis of these patients and can aid physicians when aiming to choose the optimal SBRT dose for individual patients.

Stereotactic Body Radiotherapy (SBRT) with Lower Doses for Selected Patients with Stage I Non-small-cell Lung Cancer (NSCLC).

SBRT is very effective for stage I NSCLC. Biologically effective doses (BED) >100 Gy are recommended. Elderly patients and those with a limited performance status may not tolerate these high doses. This study investigated the outcomes after lower dose SBRT (BED < 90 Gy) in 46 patients with stage I NSCLC, who were aged ≥70 years or in reduced general condition. Local control rates at 1, 2, and 3 years were 100, 95, and 95 %, respectively. Rates of freedom from distant progression were 83, 63, and 54 %, and survival rates were 77, 57, and 36 %, respectively. Seventeen patients died during the follow-up, 11 (65 %) from distant progression of NSCLC, and six (35 %) from non-malignant causes. No patient developed radiation-induced pneumonitis. Thus, SBRT with BED <90 Gy resulted in excellent local control and appears to be a reasonable option for stage I NSCLC in elderly patients and those with a poor performance status.

Excellent outcomes after radiotherapy alone for malignant spinal cord compression from myeloma.

BACKGROUND: Uncertainty exists whether patients with spinal cord compression (SCC) from a highly radiosensitive tumor require decompressive spinal surgery in addition to radiotherapy (RT). This study addressed the question by evaluating patients receiving RT alone for SCC from myeloma. PATIENTS AND METHODS: Data of 238 patients were retrospectively analyzed for response to RT and local control of SCC. In addition, the effect of RT on motor function (improvement, no further progression, deterioration) was evaluated. Overall response was defined as improvement or no further progression of motor dysfunction. Prior to RT, patients were presented to a neurosurgeon for evaluation whether upfront decompressive surgery was indicated (e.g. vertebral fracture or unstable spine). RESULTS: In the entire cohort, the overall response rate was 97% (53% improvement plus 44% no further progression). Following RT, 88% of the patients were able to walk. Of the 69 non-ambulatory patients 44 patients (64%) regained the ability to walk. Local control rates at 1, 2 and 3 years were 93%, 82% and 82%, respectively. A trend towards better local control was observed for patients who were ambulatory before starting RT (p = 0.08) and those with a more favorable performance status (p = 0.07). CONCLUSIONS: RT alone provided excellent response rates, functional outcomes and local control in patients with SCC from myeloma. These results should be confirmed in a prospective randomized trial.

A validated score estimating ambulatory status following radiotherapy of elderly patients for metastatic spinal cord compression.

BACKGROUND: This study was performed to develop a validated score predicting ambulatory status after radiotherapy (RT) alone for metastatic spinal cord compression (MSCC) in elderly patients. METHODS: 1,129 elderly patients (≥65 years) were assigned to the test (N = 565) or validation group (N = 564). In the test group, nine pre-treatment factors (age, gender, tumor type, number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval cancer diagnosis to RT, time developing motor deficits) and fractionation regimen were investigated. Factors significantly associated with post-RT ambulatory status on multivariate analysis were included in the score. The score for each factor was determined by dividing the post-RT ambulatory rate at 1 month (%) by 10. The total score represented the sum of these scores. RESULTS: In the multivariate analysis of the test group, age, primary tumor type, pre-RT ambulatory status, visceral metastases, and time developing motor deficits were significantly associated with post-RT ambulatory status. Total scores were 19 to 41 points. In the test group, post-RT ambulatory rates were 5% for 19-25 points, 35% for 26-30 points, 80% for 31-34 points, and 98% for 35-41 points (p < 0.001). 6-month survival rates were 11%, 21%, 59% and 76%, respectively. In the validation group, post-RT ambulatory rates were 4%, 33%, 77% and 98%, respectively (p < 0.001). CONCLUSIONS: Patients achieving 19-25 points had very poor functional outcomes and survival, and may receive single-fraction RT for pain relief. Selected patients with 26-34 points may benefit from additional surgery. Patients achieving ≥35 points achieved favorable results after RT alone.

Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis.

BACKGROUND: The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention. METHODS: Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox's proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance. RESULTS: On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (≤35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months). CONCLUSIONS: Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.

Setup accuracy and margins for surface-guided radiotherapy (SGRT) of head, thorax, abdomen, and pelvic target volumes.

The goal of the study was to evaluate the inter- and intrafractional patient setup accuracy of target volumes located in the head, thoracic, abdominal, and pelvic regions when using SGRT, by comparing it with that of laser alignment using patient skin marks, and to calculate the corresponding setup margins. A total of 2303 radiotherapy fractions of 183 patients were analyzed. All patients received daily kilovoltage cone-beam computed tomography scans (kV-CBCT) for online verification. From November 2019 until September 2020, patient setup was performed using laser alignment with patient skin marks, and since October 2020, using SGRT. The setup accuracy was measured by the six degrees of freedom (6DOF) corrections based on the kV-CBCT. The corresponding setup margins were calculated using the van Herk formula. Analysis of variance (ANOVA) was used to evaluate the impact of multiple factors on the setup accuracy. The inter-fractional patient setup accuracy was significantly better using SGRT compared to laser alignment with skin marks. The mean three-dimensional vector of the translational setup deviation of tumors located in the thorax, abdomen, and pelvis using SGRT was 3.6 mm (95% confidence interval (CI) 3.3 mm to 3.9 mm) and 4.5 mm using laser alignment with skin marks (95% CI 3.9 mm to 5.2 mm; p = 0.001). Calculation of setup margins for the combined inter- and intra-fractional setup error revealed similar setup margins using SGRT and kV-CBCT once a week compared to laser alignment with skin marks and kV-CBCT every other day. Furthermore, comparable setup margins were found for open-face thermoplastic masks with AlignRT compared to closed-face thermoplastic masks with laser alignment and mask marks. SGRT opens the possibility to reduce the number of CBCTs while maintaining sufficient setup accuracy. The advantage is a reduction of imaging dose and overall treatment time. Open-face thermoplastic masks may be used instead of closed-face thermoplastic masks to increase the patient's comfort.

Prognostic factors for different outcomes in patients with metastatic spinal cord compression from cancer of unknown primary.

BACKGROUND: Patients with cancer of unknown primary account for 10% of patients with metastatic spinal cord compression (MSCC). This retrospective study was performed to identify prognostic factors for functional outcome, local control of MSCC, and survival in 175 of such patients treated with radiotherapy alone. METHODS: Investigated were nine potential prognostic factors including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-radiotherapy ambulatory status, other bone metastases, visceral metastases, time developing motor deficits before radiotherapy, and the radiation schedule. RESULTS: On multivariate analysis, better functional outcome was associated with absence of visceral metastases (estimate: 0.72; 95%-confidence interval [CI]: 0.07-1.36; p = 0.030) and a slower (>7 days) development of motor deficits (estimate: 1.93; 95%-CI: 1.18-2.68; p < 0.001). Improved local control of MSCC was associated with absence of visceral metastases (risk ratio [RR]: 10.26; 95%-CI: 2.11-74.73; p = 0.004). Improved survival was associated with favorable ECOG-PS (RR: 2.12; 95%-CI: 1.40-3.29; p < 0.001), being ambulatory prior to radiotherapy (RR: 1.98; 95%-CI: 1.40-2.81; p < 0.001), absence of visceral metastases (RR: 2.74; 95%-CI: 1.93-3.91; p < 0.001), and slower development of motor deficits (RR: 1.27; 95%-CI: 1.07-1.51; p = 0.007). Absence of other bone metastases showed a trend (RR: 1.38; 95%-CI: 0.98-1.95; p = 0.07). CONCLUSIONS: This study identified additional independent prognostic factors for functional outcome, local control of MSCC, and survival after radiotherapy of MSCC from cancer of unknown primary. These prognostic factors can help select the best treatment regimen for each individual patient.

Comparison of radiochemotherapy alone to surgery plus radio(chemo)therapy for non-metastatic stage III/IV squamous cell carcinoma of the head and neck: A matched-pair analysis.

BACKGROUND AND PURPOSE: The standard treatment for non-metastatic stage III/IV squamous cell carcinoma of the head and neck varies worldwide. This study compared the outcomes of radiochemotherapy alone to surgery followed by radio(chemo)therapy (radiotherapy plus/minus concurrent chemotherapy). PATIENTS AND METHODS: Data from 148 patients treated with radiochemotherapy alone were matched to 148 patients treated with surgery plus radio(chemo)therapy. Groups were matched 1:1 for nine potential prognostic factors including age, gender, performance status, tumor site, histologic grade, T category, N category, AJCC stage, and hemoglobin level before radiotherapy, and compared for locoregional control, metastases-free survival, and overall survival. RESULTS: Locoregional control rates at 1, 2, and 3 years were 81%, 73%, and 67% after surgery plus radio(chemo)therapy and 81%, 74%, and 65% after radiochemotherapy alone (p = 0.89). Metastases-free survival rates were 86%, 80%, and 75% after surgery plus radio(chemotherapy) versus 87%, 80%, and 72% after radiochemotherapy alone (p = 0.57). Overall survival rates were 80%, 64%, and 63% after surgery plus radio(chemo)therapy versus 83%, 68%, and 60% after radiochemotherapy alone (p = 0.96). On multivariate analyses, T category (p < 0.001), N category (p = 0.004), and hemoglobin level prior to radiotherapy (p < 0.001) were associated with locoregional control. Histologic grade (p = 0.045), T category (p < 0.001), N category (p = 0.003), and hemoglobin level prior to radiotherapy (p < 0.001) were associated with metastases-free survival. Histologic grade (p = 0.030), ECOG performance status (p = 0.033), T category (p = 0.007), N category (p = 0.024) and hemoglobin level before radiotherapy (p < 0.001) were associated with overall survival. CONCLUSION: Outcomes of radiochemotherapy alone appeared similar to those of surgery plus radio(chemo)therapy. Randomized trials comparing both treatments for different tumor sites are warranted.

Dose escalation of radiotherapy for metastatic spinal cord compression (MSCC) in patients with relatively favorable survival prognosis.

BACKGROUND AND PURPOSE: Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy. PATIENTS AND METHODS: Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome. RESULTS: Local control rates at 2 years were 71% after 30 Gy and 92% after higher doses (p=0.012). Two-year progression-free survival rates were 68% and 90%, respectively (p=0.013). Two-year overall survival rates were 53% and 68%, respectively (p=0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p=0.011; p=0.012), progression-free survival (p=0.010; p=0.018), and overall survival (p=0.014; p=0.015). Functional outcome was similar in both groups. Motor function improved in 40% of patients after 30 Gy and 41% after higher doses (p=0.98). CONCLUSION: Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses.

Radiotherapy for oligometastatic disease in patients with spinal cord compression (MSCC) from relatively radioresistant tumors.

BACKGROUND: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC). Patients with relatively radioresistant tumors and oligometastatic disease may benefit from more intensive therapies (surgery, high-precision radiotherapy). If such therapies are not available, one can speculate whether patients benefit from dose escalation beyond the standard regimen 30 Gy in ten fractions. PATIENTS AND METHODS: Of 206 patients with MSCC from relatively radioresistant tumors (renal cell carcinoma, colorectal cancer, malignant melanoma), 51 had oligometastatic disease (no visceral or other bone metastases, involvement of only one to three vertebrae). In this subset, 21 patients receiving 30 Gy in ten fractions were retrospectively compared to 30 patients receiving higher doses. Seven further potential prognostic factors were investigated: age, gender, tumor type, performance status, interval from tumor diagnosis to radiotherapy of MSCC, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. RESULTS: Motor function improved in 52% of patients after 30 Gy and 40% after higher doses (p = 0.44). On multivariate analysis, functional outcome was associated with interval from tumor diagnosis to radiotherapy (p = 0.020). 1-year local control rates were 84% after 30 Gy and 82% after higher doses (p = 0.75). No factor was associated with local control. 1-year survival rates were 76% after 30 Gy and 63% after higher doses (p = 0.52). On multivariate analysis, survival was associated with performance status (p = 0.022) and interval from tumor diagnosis to radiotherapy (p = 0.039), and almost with pretreatment ambulatory status (p = 0.069). CONCLUSION: Dose escalation beyond 30 Gy in ten fractions did not improve motor function, local control, and survival in MSCC patients with oligometastatic disease from relatively radioresistant tumors.

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy.

PURPOSE: In this retrospective study, two approaches to preserve the parotid function after radiotherapy (RT) were compared: application of the radioprotective agent amifostine during RT and parotid-sparing intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: Patients were qualified for this analysis if (1) both parotid glands received a radiation dose of >or=50Gy using conventional radiotherapy techniques (cRT) or if they received a parotid-sparing IMRT as alternative, if (2) salivary gland scintigraphies before and after RT were performed, and if (3) a normal parotid function was present before RT. Quantitative salivary gland scintigraphy was used to assess the parotid gland function. RESULTS: Altogether 275 salivary gland scintigraphies of 100 patients were analyzed. The mean relative tracer uptake (DeltaU) of patients treated with cRT, cRT with amifostine and IMRT 1-12 months after RT was 0.59 (95%CI 0.54-0.65), 0.67 (95%CI 0.59-0.76), and 0.93 (95%CI 0.78-1.07), respectively. The mean relative DeltaU 13-47 months after RT was 0.40 (95%CI 0.32-0.49), 0.60 (95%CI 0.48-0.71), and 0.92 (95%CI 0.56-1.28). At 1-12 months after RT, ANOVA testing with post-hoc comparison using the Bonferroni correction showed a significant difference between IMRT and cRT (p<0.001) or IMRT and amifostine (p<0.01). The difference between amifostine and cRT was not significant during the first year. At 13-47 months after RT, the difference between cRT and amifostine was significant (p=0.02). CONCLUSION: Our data suggest that both amifostine and IMRT are able to partially preserve the parotid function after radiotherapy. The effect of IMRT appeared to be much greater.

Long-term results of a prospective multicenter phase II study to preserve the larynx function using concomitant boost radiochemotherapy with Carboplatin.

PURPOSE: This prospective phase II study was undertaken to assess the feasibility of a larynx preservation protocol with simultaneous radiochemotherapy. PATIENTS AND METHODS: Between 3/1998 and 10/2000, 42 patients with moderately advanced cancer of the larynx (n=25) and hypopharynx (n=17) eligible for total laryngectomy (LE) were treated in a prospective larynx preservation study. The study protocol scheduled 66Gy in 5 weeks using a concomitant boost technique and 70mg/m(2) Carboplatin on days 1-5 in weeks 1 and 5. RESULTS: The median follow-up time of the censored study patients was 41 months (9-95 months). The 5-year overall survival was 0.66 (95% CI 0.48-0.84), the 5-year laryngectomy-free survival 0.60 (95% CI 0.42-0.78), and the laryngeal preservation rate at 5 years 0.67 (95% CI 0.49-0.85). Cox multivariate regression analysis showed the total tumor volume to be the only statistically significant factor on locoregional failure-free survival. Six of 23 tumor-free long-term survivors received a tracheotomy because of late laryngeal toxicity associated with dysphagia 30-79 months after radiochemotherapy. CONCLUSIONS: Due to the late laryngeal toxicity observed the value of this regimen for larynx preservation is limited.

Neoadjuvant capecitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: mature results of a phase II trial.

PURPOSE: The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting. PATIENTS AND METHODS: 96 patients (63% male, age 34-81 years) with advanced rectal cancer (cT3-4 or cN+) from seven university centers in Germany were recruited. All were to receive a total irradiation dose of 50.4-55.8 Gy with conventional fractions. Capecitabine was given at an oral dosage of 825 mg/m(2)bid on each day of the radiotherapy period with the first daily dose applied 2 h before irradiation, followed by surgery 6 weeks later. RESULTS: Most of the patients suffered from an advanced primary tumor (cT3: 57%, cT4: 40%) with lymph node involvement in 60%. After neoadjuvant treatment, with a mean of 99% of the scheduled radiation dose actually delivered, a clinical response rate of 68% (95% confidence interval: 57-78%) was observed. Out of 87 evaluable patients undergoing surgery, a sphincter-preserving procedure could be performed in 51% and R0 resection in 94%. A pathologically complete response was achieved in six patients (7%, 95% confidence interval: 3-14%). The comparison of initial diagnosis and pathologic findings showed a downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade >/= 3 included lymphopenia (12%), leukopenia (6%), and diarrhea (7%). Mild to moderate hand-foot syndrome occurred in 12% only. After a median follow-up of 48 months, the 5-year overall survival and tumor control data were, with regard to patient selection, in the expected range with an overall survival of 65%, a relapse-free survival of 47%, and a local recurrence rate after 5 years of 17%. CONCLUSION: The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradiation of rectal cancer with a favorable safety profile.

1x8 Gy versus 5x4 Gy for metastatic epidural spinal cord compression: a matched-pair study of three prognostic patient subgroups.

BACKGROUND: This study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses. METHODS: Patients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included. RESULTS: In poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function. CONCLUSIONS: Since in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.

Comparison of Two Radiotherapy Regimens for Metastatic Spinal Cord Compression: Subgroup Analyses from a Randomized Trial.

BACKGROUND/AIM: According to our randomized trial, 5×4Gy was comparable to 10×3Gy for metastatic spinal cord compression. Since it remained unclear whether findings applied to poor and intermediate prognoses patients, subgroup analyses were performed. PATIENTS AND METHODS: In patients with poor prognoses, 58 received 5×4Gy, 53 received 10×3Gy. In intermediate-prognoses patients, numbers were 43 and 49. RESULTS: In patients with poor prognoses, 1-month overall response (OR) was 85% after 5×4Gy and 10×3Gy (p=0.99), improvement 38% vs. 42%, ambulatory status 60% vs. 64% (p=0.83), 6-month local progression-free survival (LPFS) 75% vs. 69% (p=0.74) and 6-month overall survival (OS) 26% vs. 19% (p=0.43). In patients with intermediate prognoses, 1-month OR was 89% after 5×4Gy and 93% after 10×3Gy (p=0.85), improvement 39% vs. 45%, ambulatory status 84% vs. 82% (p=0.90), 6-month LPFS 79% vs. 92% (p=0.17) and 6-months OS 65% vs. 58% (p=0.65). CONCLUSION: 5×4Gy was not significantly inferior to 10x3Gy in both subgroups.