Christoph Glanzmann

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). 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. 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. The NLR remains an independent prognostic factor for patients with OC undergoing radiotherapy independent of the tumor volume.

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. 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). 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. Acceleration of the START A regime with 41.6 Gy WBI plus additional boost of 9-12 Gy remained effective and well-tolerated.

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.

To evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT. 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. 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. 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.

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. 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). 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. 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.

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. 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. 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. 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.

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.

Former prospective analyses revealed gross tumor volume (GTV) as the most reliable parameter to statistically significantly predict disease control in head neck cancer (HNC) patients treated with definitive intensity modulated radiation therapy (IMRT) +/-concomitant systemic therapy. The most 'unfavourable' subgroup was characterized by total GTV (tGTV) of > 70 cc, translating in ~50 and 65% 3-year disease free (DFS) and overall survival (OAS, vs 68% and 88% in tGTV < 70 cc, p = 0.001 and 0.0001), and ~25% distant spread (vs 6% for tGTV < 70 cc, p < 0.0001).