Single-Institution Prospective Evaluation of Moderately Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Integrated Boost With or Without Lymphatic Drainage Irradiation After Breast-Conserving Surgery.

Purpose: We report treatment outcomes for patients who received adjuvant moderate hypofractionated whole-breast radiation therapy with simultaneous integrated boost (SIB-mhWBRT) after breast-conserving surgery. Methods and Materials: SIB-mhWBRT for patients with breast cancer was introduced in our department in July 2017. This prospective evaluation includes 424 consecutive patients treated with SIB-mhWBRT for stage I-III invasive breast cancer (n = 391) and/or ductal carcinoma in situ (n = 33) until December 2021. SIB-mhWBRT was applied with 40 Gy in 15 daily fractions over 3 weeks according to the START B trial, with an SIB dose to the tumor bed of 48 Gy according to Radiation Therapy Oncology Group 1005/UK-IMPORT-HIGH, delivered as 3-dinemsional conformal radiation therapy (RT; n = 402), intensity modulated RT (n = 4), or volumetric modulated arc therapy (n = 18). The mean patient age was 60 years (range, 27-88). Since May 2018, patients with indications for lymphatic pathway RT were included (n = 62). Baseline parameters and follow-up data were recorded and reported, including objective assessment of treatment-related outcomes and subjective patient-reported outcome measures (PROMs). Results: Mean/median follow-up was 29/33 months (range, 2-60). Acute toxicity grade 0, 1, 2, and 3 was observed in 25.0%, 61.4%, 13.3%, and 0%, respectively, at the completion of RT. Data of 281, 266, 243, 172, and 58 patients were available for 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Grade 2 late effects were identified in 8.5%, 6.0%, 4.9%, 2.2%, and 10.2% and grade 3 in 2.8%, 1.1%, 1.2%, 0%, and 0% of patients at 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Medical treatment of breast edema was the only grade 3 late effect observed. PROM cosmesis results were evaluated as excellent-good, fair, and poor in 97.2%, 2.5%, and 0.4%; 96.5%, 3.1%, and 0.4%; 97.4%, 2.2%, and 0.4%; 97.5%, 2.5%, and 0%; and 96.5%, 3.5%, and 0.0% at 6 months and 1, 2, 3, and 4 years post-RT, respectively. For all patients, the 3-year overall, cancer-specific, and disease-free survival rates were 98.2%, 99.1%, and 95.9%, respectively. Three-year risk of any locoregional recurrence was 0.6%. No mortality or relapse was observed in patients with ductal carcinoma in situ. Conclusions: SIB-mhWBRT demonstrated very favorable side effect profiles and cosmesis/PROMs. Three-year results demonstrate excellent locoregional control. This short-term regimen offers substantial patient comfort and improves institutional efficacy.

Early and Intermediate Treatment Outcome After Postoperative External Beam Accelerated Partial Breast Irradiation in Patients With Early-Stage Breast Cancer.

PURPOSE: To prospectively evaluate early and intermediate outcome after accelerated partial breast irradiation (APBI) in patients early-with stage breast cancer. METHODS AND MATERIALS: Inclusion criteria were defined according to the APBI American Society for Radiation Oncology's ASTRO Evidence-Based Consensus Statement. The prescribed dose was 26 to 28 Gy in 5 fractions on 5 consecutive days. Regular follow-up visits with objective and subjective evaluation of treatment tolerance were performed after 0 and 2 weeks, 6 months, and at annual intervals. RESULTS: Between February 2017 and January 2020, 175 patients with breast conserving surgery met the inclusion criteria for APBI. Mean age was 65.7 years (range, 46-88). Thirteen percent of patients received a diagnosis with carcinoma in situ, 55%, 35%, and 37% with T1a/b/c, and 10% with T2 stages, respectively. The mean volume of planning target volume (PTV) was 119 cc (range, 45-465), the ratio of mean PTV: whole breast volume ratio was 21% (7%-53%). Mean follow-up was 42 months (median, 45, range, 0-67). Acute toxicity after 2 weeks was low with 69%, 26%, and 5% grade 0, 1, and 2. In addition, 1-, 2-, 3-, 4-, and 5-year follow-up data were available from 146, 134, 107, 73, and 25 patients. Patient-reported cosmetic outcomes were assessed excellent or good in 97.9%, 98.5%, 98.1%, 98.6%, and 100%. Regarding grade 2 toxicities, as by now 3%, 2%, 2%, 0%, and 0% G2 fibrosis, 1%, 1%, 0%, 0%, and 0% G2 atrophy, no G2 skin telangiectasia or breast edema occurred. So far, none of the patients have experienced G3 toxicity or higher. The remaining patients had grade 0 or 1 toxicity only. Five ipsilateral breast recurrences (1 marginally to PTV, 4 out-of-field) and 5 distant recurrences were recorded by March 2023. The 4-year in-breast recurrence rate was 2.5%. Eight patients died, with 2 of them from disease. For all patients, the 4-year overall, cancer specific and disease-free survival rates were 97.1%, 99.4%, and 95.3%, respectively. CONCLUSIONS: We showed high early- and intermediate-term treatment tolerance and disease control of APBI using 26 to 28 Gy in five fractions in one week in carefully selected patients with early breast cancer. APBI is highly appreciated by patients and efficient, as an additional advantage for busy centers.

[Radiation Oncology - Recent Status]. / Krebsbehandlung: aktueller Stand der perkutanen Strahlentherapie.

Radiation Oncology - Recent Status Abstract. We summarize the most important developments and innovations in the field over the past years and illustrate resulting external radiation treatment schedules and related treatment tolerance, focusing on hypofractionation.

Consolidation cetuximab after concurrent triplet radiochemotherapy+cetuximab in patients with advanced head and neck cancer: A randomized phase II study.

BACKGROUND AND PURPOSE: Preclinical data suggest that cetuximab should be continued after end of concurrent radiotherapy+cetuximab due to its efficacy against residual tumor cells in the irradiated tumor bed. Based on this concept the phase II add-on cetuximab (AOC) study was designed. MATERIALS AND METHODS: Altogether 63 patients with advanced head and neck cancer were treated with radiochemotherapy (70 Gy, cisplatin 40 mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400 mg/m2, then 250 mg/m2 weekly). Thereafter patients were randomized to cetuximab consolidation (500 mg/m2 biweekly × 6) or no further treatment. The primary endpoint was the 2-year locoregional control (LRC) rate. As translational research endpoints serum markers were analyzed before and during treatment and CT-based quantitative image analysis (radiomics) was performed. RESULTS: Median follow-up was 24 months. The 2-year LRC rates were 67.9% and 67.7% in the treatment arms with and without consolidation cetuximab, respectively. Higher than median levels of three serum markers were negatively associated with the 2-year LRC rate in the overall patient cohort: Osteopontin, IL8 and FasL2 (p ≤ 0.05). A radiomics model consisting of two radiomics features could be built showing that higher entropy and higher complexity of tumor Hounsfield unit distribution indicates worse LRC (concordance index 0.66). No correlation was found between biological and imaging markers. CONCLUSIONS: There was no evidence that consolidation cetuximab would improve the 2-year LRC rate. Prognostic biological and imaging markers could be identified for the overall patient cohort. Studies with larger patient numbers are needed to correlate biological and imaging markers.

Neutrophil-lymphocyte ratio complements volumetric staging as prognostic factor in patients treated with definitive radiotherapy for oropharyngeal cancer.

BACKGROUND: Volumetric tumor staging has been shown as superior prognostic tool compared to the conventional TNM system in patients undergoing definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer. Recently, clinical immunoscores such as the neutrophil-lymphocyte ratio (NLR) have been investigated as prognostic markers in several tumor entities. The aim of this study was to assess the combined prognostic value of NLR and tumor volume in patients treated with IMRT for oropharyngeal cancer (OC). METHODS: Data on all consecutive patients treated for locally advanced or inoperable OC with IMRT from 2002-2011 was prospectively collected. Tumor volume was assessed based on the total gross tumor volume (tGTV) calculated by the treatment planning system volume algorithm. The NLR was collected by a retrospective analysis of differential blood count before initiation of therapy. RESULTS: Overall, 187 eligible patients were treated with a median IMRT dose of 69.6 Gy. Three-year recurrence-free survival (RFS) for low, intermediate, high and very high tumor volume groups was 88%, 74%, 62% and 25%, respectively (p = 0.007). Patients with elevated NLR (>4.68) showed a significantly decreased 3-year RFS of 44% vs. 81% (p < 0.001) and 3-year OS of 56% vs. 84% (p < 0.001). The NLR remained a significant prognostic factor for RFS and OS when tested among tumor volume groups. Univariate and multivariate regression analysis confirmed both tumor volume and NLR as independent prognostic factors. The NLR offered further statistically significant prognostic differentiation of the small/intermediate/large tumor volume groups. CONCLUSION: The NLR remains an independent prognostic factor for patients with OC undergoing radiotherapy independent of the tumor volume.

Local control and intermediate-term cosmetic outcome following IMRT for nasal tumors : An update.

OBJECTIVE: This study aims to evaluate local control and intermediate-term cosmetic outcome in patients with cancer of the nose treated with intensity-modulated radiotherapy (IMRT). METHODS: From June 2008 to September 2015, 36 consecutive patients presenting with nasal cavity, ala of the nose, or nasal vestibule tumors were treated at the Department of Radiation Oncology, University Hospital Zurich either postoperatively (n = 14; 3/14 with nasal ablation) or with definitive IMRT (n = 22). Of these 36 patients, 8 presented with recurrent disease after surgery only and 1/36 with N1 disease. Concurrent systemic therapy was administered in 18/36 patients (50%). Nasal follow-up (FU) imaging documentation of 13 patients with preserved organ and >6 months FU offers a pre/post IMRT FU comparison. In addition, these patients' subjective evaluation of cosmesis was assessed. RESULTS: Mean/median FU was 41/33 months (range 5-92 months). Salvage ablation with curative intent was undergone by 3 patients with local relapse after definitive (n = 2) and postoperative (n = 1) IMRT. The 3­year local control, ultimate local control, and overall survival rates were 90, 97, and 90 %, respectively. Subjective and objective cosmetic outcome after IMRT is very satisfying so far. CONCLUSION: IMRT for nasal tumors was found to be effective and well tolerated. Intermediate-term cosmetic results are good. Radical surgical procedures may be saved for curative salvage treatment.

IMRT/VMAT for malignancies in the head-and-neck region : Outcome in patients aged 80.

OBJECTIVE: Elderly patients with malignant head-and-neck tumors (HNT) often pose a therapeutic challenge. They frequently have significant comorbidities which may influence their ability to tolerate tumor-specific therapies. Our aim was to investigate the outcome of patients aged 80+ years undergoing curative intent intensity- or volume-modulated radiation therapy (IMRT/VMAT). METHODS: We retrospectively reviewed our HNT patients aged 80+ treated with curative IMRT/VMAT from December 2003 to November 2015. Overall survival (OS), disease-free survival (DFS), local control (LC), and treatment tolerance were assessed. Outcome results were compared with that of a younger HNT patient cohort from our hospital. RESULTS: A total of 140 consecutive patients were included (65 postoperative, 75 definitive). Mean/median age at treatment start was 84.8/84.1 years (range 80-96 years). Mean/median follow-up time was 25/16 months (range 2-92 months). Of the 140 patients, 80 were alive with no evidence of disease when last seen, 28 had died due to the cancer, 12 remained alive with disease, the remaining 20 died intercurrently. Systemic concomitant therapy was administered in 7 %. Late grade 3-4 toxicity was observed in 2 %. All patients completed treatment. Hospitalization and feeding tube rates were 26 % and 11 %, respectively. The 2­/3-year LC, DFS, and OS rates for the entire cohort were 81/80 %, 69/63 %, and 68/66 %, respectively. Squamous cell carcinoma (SCC) patients showed an inferior 3-year OS rate as compared to non-SCC patients (62 % vs 77 %, p = 0.0002), while LC and DFS did not differ. Patients undergoing postoperative radiation attained a higher OS compared to the definitively irradiated subgroup with 74 vs. 60 % at 3 years (p = 0.01); however, DFS rates were similar for both groups (68 vs. 61 %, p = 0.15). Corresponding rates for >1400 HNT patients <80 years treated during the same time interval were 81/80 %, 69/67 %, and 77/72 %, respectively. CONCLUSIONS: Treatment tolerance in our patients aged 80+ was high. These results suggest that elderly HNT patients should not be denied potentially curative treatment strategies.

Hypofractionated Radiotherapy for Breast Cancer Including Risk-adapted Boost: Update on Tolerance and Efficacy of an Accelerated START A Regime.

AIM: To present an update of a prospective study evaluating an accelerated hypofractionated whole breast irradiation (WBI) schedule of the START A trial plus hypofractionated boost in breast cancer patients. PATIENTS AND METHODS: One hundred and forty consecutive patients ≥55 years were included in this study. Patients received postoperative WBI with 13×3.2 Gy to 41.6 Gy plus a boost of 3.0 Gy/fraction to 9-12 Gy applied in <3.5 weeks, depending on the resection margin. Prospectively planned follow-up (FU) visits, including objective and subjective assessment of treatment tolerance, were performed at 0 and 8 weeks, as well as one, two, four or more years following radiotherapy (RT). RESULTS: The 3-year rates of local control, nodal control, disease-free and overall survival were 99%, 100%, 96% and 91%, respectively. Cosmetic outcome was very good with 99% (n=110/111), 98% (n=99/101) and 100% (n=59/59) of the patients being satisfied or very satisfied one, two and four years after RT, respectively. CONCLUSION: Acceleration of the START A regime with 41.6 Gy WBI plus additional boost of 9-12 Gy remained effective and well-tolerated.

Risk profile for osteoradionecrosis of the mandible in the IMRT era.

BACKGROUND: The risk for osteoradionecrosis (ORN) of the mandible is positively related to bone volume exposed to > ~ 60 Gy. We hypothesized that in combined treatment, surgery may also be a risk factor. PATIENTS AND METHODS: The impact of mandibular surgery on ORN in locally disease-free IMRT cohorts was retrospectively analyzed. RESULTS: Between October 2002 and October 2013, 531 of 715 patients with oral cavity cancer (OCC), mesopharyngeal cancer (MC), or salivary gland tumor were treated with the mandible bone exposed to ~ > 60 Gy (mean follow-up, 38 months; 7-143 months). Of the 531 patients, 36 developed ORN (7 %; 1.5 % with grade 3-4). The ORN rate in definitive IMRT MC (16/227) and in postoperative IMRT OCC patients with no mandibular surgery (3/46) was 7 % each; in OCC patients with mandibular surgery the rate was 29 % (15/60, p = 0.002). Marginal or periosteal bone resection was found to be a high risk factor (39 %, vs. 7 % followed by segmental or no resection, p < 0.0001). CONCLUSION: Marginal or periosteal bone resection of the mandible was identified as the highest ORN risk factor in our IMRT cohort.

Less may be more: nodal treatment in neck positive head neck cancer patients.

Ongoing debates about the need and extent of planned neck dissection (PND), and required nodal radiation doses volumes lead to this evaluation. Aim was to assess nodal control after definitive intensity modulated radiation therapy (IMRT ± systemic therapy) followed by PND in our head neck cancer cohort with advanced nodal disease. Between 01/2005 and 12/2013, 99 squamous cell cancer HNC patients with pre-therapeutic nodal metastasis ≥3 cm were treated with definitive IMRT followed by PND. In addition, outcome in 103 patients with nodal relapse after IMRT and observation only (no-PND cohort) were analyzed. Prior to PND, PET-CT, fine needle aspirations, ultrasound and palpation were assessed regarding its predictive value. Patterns of nodal relapse were assessed in patients with isolated neck failure after definitive IMRT alone. 70/99 (70 %) PND specimens showed histopathological complete response (hCR), which translated into statistically significantly superior survival compared with partial response (hPR) with 4-year overall survival, disease specific survival and nodal control rates of 90/83/96 vs 67/60/78 % (p = 0.002/0.001/0.003). 1/99 patient developed isolated subsequent nodal disease. 64/2147 removed nodes contained viable tumor (3 %). Predictive information of the performed diagnostic investigations was not reliable. 17/70 hCR patients showed true negative findings in available three to four investigations (0/29 hPR). 27/103 no-PND patients developed isolated neck disease (26 %) with successful salvage in 21/24 [88 %, or 21/27 (78 %)]. Nearly all failures occurred in the prior nodal gross tumor volume area. A more restrictive approach regarding PND and/or nodal IMRT dose-volumes may be justified.

Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.

BACKGROUND: The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS: We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS: Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

Radiation-induced lower cranial nerve palsy in patients with head and neck carcinoma.

Radiation-induced cranial nerve palsy (RICNP) is a severe long-term complication in patients with head and neck cancer following high-dose radiation therapy (RT). We present the case report of a patient with bilateral RICNP of the hypoglossal and vagus cranial nerves (XII/X) following postoperative RT in the era prior to the introduction of intensity-modulated RT (IMRT), and an analysis of our IMRT patient cohort at risk including the case of a XII RICNP. A total of 201 patients whose glosso-pharyngeal (IX), X and XII cranial nerves had been exposed to >65 Gy definitive IMRT in our institution between January, 2002 and December, 2012 with or without systemic therapy, were retrospectively identified. A total of 151 patients out of 201 fulfilling the following criteria were included in the analysis: Locoregionally controlled disease, with a follow-up (FU) of >24 months and >65 Gy exposure of the nerves of interest. So far, one of the assessed 151 IMRT patients at risk exhibited symptoms of RICNP after 6 years. The mean/median FU of the entire cohort was 71/68 months (range, 27-145). The results were compared with literature reports. In conclusion, RICNP appears to be a rare complication. However, a longer FU and a larger sample size are required to draw reliable conclusions on the incidence of RICNP in the era of IMRT.

Carotid artery disease after head and neck radiotherapy.

Radiation induced atherosclerosis of the carotid artery is a clinically relevant late complication after head and neck radiotherapy. Improved long-term survival after multimodality therapy in neck malignancies result in an increased risk of carotid artery disease in patients after radiotherapy (RT). This review focuses on the current knowledge of occlusive carotid disease after head and neck radiotherapy and highlights the exceeding morphologic post-radiation vessel wall pathologies. More severe and extensive carotid artery atherosclerosis with plaque in all segments including the common carotid artery is a frequent finding after RT. Therefore, colour coded duplex ultrasound surveillance in patients after head and neck RT is recommended. Some histopathological studies indicate differences to “classical” atherosclerosis, and pathogenesis of chronic radiation vasculopathy is still under discussion.

PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers.

PURPOSE: To evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT. PATIENTS AND METHODS: Between 2009 and 2012, 20 patients with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were treated with VMAT in supine position with fiducial markers (FM), endorectal balloon (ERB) and full bladder. CBCT's and kV/kV imaging were performed before and additional CBCT's after treatment assessing intra-fraction motion. CTVP for 5 patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were contoured independently by 3 radiation oncologists using MRI. The van Hark formula (PTV margin =2.5Σ +0.7σ) was applied to calculate PTV margins of prostate/seminal vesicles (P/PSV) using CBCT or FM. RESULTS: 172 and 52 CBCTs before and after RT and 507 kV/kV images before RT were analysed. Differences between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm). Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5 mm). Patient positioning using bone matching or ERB-matching resulted in larger PTV margins. CONCLUSIONS: For IGRT CBCT or kV/kV-image pairs with FM are interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV margins can be kept in the range of 5 mm or below if stringent daily IGRT, ideally including prostate tracking, is applied. MR-based CTV delineation optimization is recommended.

Clinical experience of SIB-IMRT in anal cancer and selective literature review.

PURPOSE: To evaluate feasibility and outcome of our institutional SIB-IMRT schedule in patients with anal cancer and to selectively review the literature on different SIB-IMRT schedules. PATIENTS AND METHODS: Between 01/08-06/13 25 patients with biopsy proven squamous cell anal cancer were treated in our institution with IMRT. Radiotherapy was delivered in two series using a SIB-IMRT schedule of 45 Gy/1.8 Gy to the primary tumor and adjacent pelvic lymph nodes and 38 Gy/1.52 Gy to elective nodes followed by an IMRT boost of 7×2 Gy = 14 Gy to the primary tumor and involved nodes (cumulative prescription dose: 59 Gy). RESULTS: Mean follow-up was 20 months (range: 4-68). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival rates were 92%, 92%, 92%, and 88%, respectively. Grade 3 acute skin toxicity was observed in 6 patients (24%). No high grade gastrointestinal or urinary acute toxicity occurred. Four patients required more than one day of treatment interruption due to acute toxicity. No grade 3 or higher late sequelae were observed. CONCLUSION: We present our institutional SIB-IMRT experience treating patients with anal cancer in two series using moderate single doses from 1.5-2.0 Gy. Our results, in terms of loco-regional outcome and toxicity, were comparable to other studies. The incidence of treatment interruptions was very low. Therefore this schedule appears to be safe for clinical use.

Hypofractionated radiotherapy for breast cancer acceleration of the START A treatment regime: intermediate tolerance and efficacy.

PURPOSE: Prospective evaluation of accelerated hypofractionated radiotherapy (RT) in breast cancer patients treated with 41.6 Gy in 13 fractions plus boost delivered five times a week. PATIENTS AND METHODS: Between 03/2009 and 10/2012 98 consecutive patients aged >55 years presenting with breast cancer (invasive cancer: n = 95, ductal carcinoma in situ (DCIS): n = 3) after breast conserving surgery were treated in our institution with the following schedule: 41.6 Gy in 13 fractions 4 times a week and 9 or 12 Gy boost in 3 or 4 fractions (on day 5 each week), cumulative dose: 50.6 Gy in 3.2 weeks or 53.6 Gy in 3.4 weeks, respectively depending on resection status. 56 patients had a T1 tumor, 39 a T2 tumor. N-status was as follows: N0: n = 71, N1: n = 25, N2/3: n = 2. 23 patients (24%) received chemotherapy before RT. A prospectively planned follow-up (FU) visit with objective and subjective assessment of treatment tolerance (questionnaires) was performed 0 and 8 weeks after RT completion, and one, two and four years later, respectively. RESULTS: Mean/median follow-up was 32/28 months (range: 12-56). After 2 years local control, loco-regional control and disease-free survival was 100%, 100%, and 98%, respectively. Overall survival was 96% at 2 years. Cosmetic outcome was very good with patients being satisfied or very satisfied in 99% (n = 86/87), 97% (n = 55/57) and 100% (n = 25/25) after one, two and four years after RT, respectively. No grade ≥ 2 pain was described in the 25 patients with a FU of at least 4 years. Fibrosis, telangiectasia and edema were found in 7-15%, 0-22% and 0-11% at one, two, and four years, respectively, and are comparable to other trials. CONCLUSION: The applied hypofractionated RT regime with single doses of 3.2 Gy plus boost doses of 9-12 Gy in 3-4 fractions applied in 5 sessions a week was effective and well tolerated on intermediate term FU.

Risk-adapted partial larynx and/or carotid artery sparing modulated radiation therapy of glottic cancer.

BACKGROUND: To evaluate outcome in patients with glottic cancer treated with intensity-modulated radiotherapy (IMRT) and to show effectiveness of partial laryngeal- and/or carotid artery sparing in low to intermediate risk tumors. STUDY DESIGN: Retrospective analysis. MATERIAL AND METHODS: From 01/2004 to 03/2013 77 consecutive patients presenting with glottic cancer were treated in our department with IMRT as definitive treatment. T-stages distributed as follows: T1: n = 17, T2: n = 24, T3: n = 15, T4: n = 13 and recurrences: 8 patients. Concomitant systemic therapy was applied in 39 patients consisting of either cisplatin or cetuximab. RESULTS: Mean/median follow-up (FU) time was 32.2/28 months (range: 4-98.7). Three year local control (LC), ultimate LRC and laryngectomy free survival rate was 77%, 92% and 80%, respectively. Three year overall survival of the entire cohort was 81%. Three year local control for T1/T2, T3/T4, and recurred tumors was 95%, 65%, and 38%, respectively. Three year overall survival was 86% for T1-4 stages, 55% for recurred disease, respectively. Partial laryngeal/carotid artery sparing was performed in all T1 patients (n = 17) and 17/22 T2N0 patients. Rate of late sequels was low. CONCLUSION: IMRT for glottic cancer shows high control rates. In low to intermediate risk tumors an individualized treatment volume with partial larynx +/- carotid artery sparing is effective and holds the potential to reduce long term toxicity. The therapeutic outcome was not compromised.

Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study.

BACKGROUND: EORTC trial 22921 examined the addition of preoperative or postoperative chemotherapy to preoperative radiotherapy in patients with rectal cancer. After a median follow-up of 5 years, chemotherapy-irrespective of timing-significantly improved local control. Adjuvant chemotherapy did not improve survival, but the Kaplan-Meier curves diverged, suggesting possible delayed benefit. Here, we report the updated long-term results. METHODS: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy with or without concomitant chemotherapy before surgery followed by either adjuvant chemotherapy or surveillance. Randomisation was done using minimisation with factors of institution, sex, T stage, and distance from the tumour to the anal verge. Study coordinators, clinicians, and patients were aware of assignment. Radiotherapy consisted of 45 Gy to the posterior pelvis in 25 fractions of 1·8 Gy over 5 weeks. Each course of chemotherapy consisted of fluorouracil (350 mg/m(2) per day intravenous bolus) and folinic acid (leucovorin; 20 mg/m(2) per day intravenous bolus). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. The primary endpoint was overall survival. This analysis was done by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00002523. FINDINGS: 1011 patients were randomly assigned to treatment between April, 1993, and March, 2003 (252 to preoperative radiotherapy and 253 to each of the other three groups). After a median follow-up of 10·4 years (IQR 7·8-13·1), 10-year overall survival was 49·4% (95% CI 44·6-54·1) for the preoperative radiotherapy group and 50·7% (45·9-55·2) for the preoperative radiotherapy and chemotherapy group (HR 0·99, 95% CI 0·83-1·18; p=0·91). 10-year overall survival was 51·8% (95% CI 47·0-56·4) for the adjuvant chemotherapy group and 48·4% (43·6-53·0) for the surveillance group (HR 0·91, 95% CI 0·77-1·09, p=0·32). 10-year disease-free survival was 44·2% (95% CI 39·5-48·8) for the preoperative radiotherapy group and 46·4% (41·7-50·9) for the preoperative radiotherapy and chemotherapy group (HR 0·93, 95% CI 0·79-1·10; p=0·38). 10-year disease-free survival was 47·0% (95% CI 42·2-51·6) for the adjuvant chemotherapy group and 43·7% (39·1-48·2) for the surveillance group (HR 0·91, 95% CI 0·77-1·08, p=0·29). At 10 years, cumulative incidence of local relapse was 22·4% (95% CI 17·1-27·6) with radiotherapy alone, 11·8% (7·8-15·8) with neoadjuvant radiotherapy and chemotherapy, 14·5% (10·1-18·9) with radiotherapy and adjuvant chemotherapy and 11·7% (7·7-15·6) with both adjuvant and neoadjuvant chemotherapy (p=0·0017). There was no difference in cumulative incidence of distant metastases (p=0·52). The frequency of long-term side-effects did not differ between the four groups (p=0·22). INTERPRETATION: Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or without chemotherapy) does not affect disease-free survival or overall survival. Our trial does not support the current practice of adjuvant chemotherapy after preoperative radiotherapy with or without chemotherapy. New treatment strategies incorporating neoadjuvant chemotherapy are required. FUNDING: EORTC, US National Cancer Institute, Programme Hospitalier de Recherche Clinique, Ligue contre le Cancer Comité du Doubs.

Late term tolerance in head neck cancer patients irradiated in the IMRT era.

BACKGROUND: The aim was to quantify severe transient and persisting late term effects in our single institution head neck cancer (HNC) cohort treated with curatively intended intensity modulated radiation therapy (IMRT). Hypothesis was if a 2-year follow up (FU) is sufficient to estimate the long term tolerance in HNC irradiated in the IMRT era. METHODS: Between 01/2002-8/2012, 707/1211 (58%) consecutively treated IMRT patients met the inclusion criteria of a FU time >12 months and loco-regional disease control (LRC). 45% presented with loco-regionally advanced disease; 55% were referred for curative definitive IMRT (66 Gy-72 Gy in 30-35 fractions), 45% underwent postoperative IMRT (60-66 Gy in 30-33 fractions). Systemic concomitant therapy was administered in 85%. Highly consistent treatment procedures were performed with respect to contouring processes, dose constraints, radiation schedules, and the use of systemic therapy. Grade 3/4 late term effects were prospectively assessed and analyzed with respect to subgroups at particular risk for specific late effects. RESULTS: Mean/median FU of the cohort was 41/35 months (15-124). 13% of the patients (92/707) experienced any grade 3/4 late effects (101 events in 92/707 patients), 81% in the first 12 months after radiation. 4% of all developed persisting late grade 3/4 effects (25 events in 25/707 patients). CONCLUSIONS: IMRT led to a high late term tolerance in loco-regionally disease free HNC patients. The onset of any G3/4 effects showed a plateau at 2 years. The question of the cervical vessel tolerance in disease free long time survivors is still open and currently under evaluation at our institution.