Local control and survival after stereotactic body radiation therapy of early-stage lung cancer patients in Slovenia.

BACKGROUND: Stereotactic body radiation therapy (SBRT) precisely and non-invasively delivers ablative radiation dose to tumors in early-stage lung cancer patients who are not candidates for surgery or refuse it. The aim of research was to evaluate local control, overall survival (OS), local progression free survival (LPFS), distant metastases free survival (DMFS), disease free survival (DFS) and toxicity in early-stage lung cancer patients treated with SBRT in a single tertiary cancer centre. PATIENTS AND METHODS: We retrospectively evaluated medical records and radiation treatment plan parameters of 228 tumors irradiated in 206 early-stage lung cancer patients between 2016 and 2021 at the Institute of Oncology Ljubljana. RESULTS: After 25 months of median follow up, 68 of 206 (33%) patients died. Median OS was 46 months (CI 36-56), 1-year, 2-year and 3-year OS were 87%, 74% and 62% and 5-year OS was 31%. A total of 45 disease progressions have been identified in 41 patients. Local progress only was noticed in 5 (2%) patients, systemic progress in 32 (16%) and combined systemic and local in 4 (2%) patients. Local control rate (LCR) at 1 year was 98%, at 2 and 3 years 96% and 95% at 5 years. The 1-, 2- and 3-year LPFS were 98%, 96% and 94%, respectively and 5-year LPFS was 82%. One, 2-, 3- and 5-year DFS were 89%, 81%, 72% and 49%, respectively. Among 28 toxicities recorded only one was Grade 4 (pneumonitis), all others were Grade 1 or 2. No differences in LCR, LPFS, DFS were found in univariate analysis comparing patient, tumor, and treatment characteristics. For OS the only statistically significant difference was found in patients with more than 3 comorbidities compared to those with less comorbidities. CONCLUSIONS: Early lung cancer treated with SBRT at single tertiary cancer centre showed that LCR, LPFS, DFS, DMFS and OS were comparable to published studies. Patients with many comorbidities had significantly worse overall survival compared to those with less comorbidities. No other significant differences by patient, tumor, or treatment characteristics were found for DMFS, LPFS, and DFS. Toxicity data confirmed that treatment was well tolerated.

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.

The spine and carina as a surrogate for target registration in cone-beam CT imaging verification in locally advanced lung cancer radiotherapy.

BACKGROUND: The aim of the study was to evaluate the accuracy of volumetric lung image guidance using the spine or carina as a surrogate to target for image registration, as the best approach is not established. PATIENTS AND METHODS: Cone beam computed tomography images from the 1st, 10th, 15th, and 20th fraction in 40 lung cancer patients treated with radical radiotherapy were retrospectively registered to planning CT, using three approaches. The spine and carina alignment set-up deviations from a reference (tumour/lymph nodes) registration in the lateral (LAT), longitudinal (LONG) and vertical (VRT) directions were analysed and compared. Tumour location and nodal stage influence on registration accuracy were explored. RESULTS: The spine and carina mean set-up deviation from reference were largest in the LONG, with the best match in the VRT and LAT, respectively. Both strategies were more accurate in central tumours, with the carina being more precise in 50% LAT and 66% LONG mean deviations. For all measurements in all patients a carina vs. spine registration comparison showed improved carina accuracy in LAT and LONG. In comparative subgroup analysis the carina was superior compared to spine in LAT and LONG in centrally located tumours, N2 and N3. Both strategies were comparable for peripheral tumours and N0. CONCLUSIONS: Carina registration shows greater accuracy compared to spine in the LAT and LONG directions and is superior in central tumours, N2 and N3. The spine and carina surrogates are equally accurate for peripheral tumours and N0. We propose the carina as a surrogate to target for CBCT image registration in locally advanced lung cancer.

Preoperative intensity-modulated chemoradiotherapy with simultaneous integrated boost in rectal cancer: five-year follow-up results of a phase II study.

BACKGROUND: We conducted a phase II study to investigate the feasibility and safety of preoperative radiochemo-therapy experimental fractionation, using intensity-modulated radiation therapy with simultaneous integrated boost (IMRT SIB) to shorten the overall treatment time without dose escalation in intermediate/locally advanced rectal cancer with the aim to improving treatment outcome. PATIENTS AND METHODS: A total of 51 patients with operable stage II-III rectal carcinoma were included between January 2014 and January 2015. Fifty patients completed preoperative IMRT treatment with an elective dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/T3 and 48.4 Gy to T4 tumour in 22 fractions, with concomitant capecitabine (825 mg/m2/12 h, including at weekends). Median follow-up was 70 months (range 11-80 m). RESULTS: Forty-seven patients completed treatment per protocol. Acute toxicity occurred in 2 (4%) patients. R0 resection was achieved in all but 1 and pathologic complete response (pCR) in 12 (25.5%) patients who had 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) of 91.7%, 100% and 100%, respectively. The intention-to-treat analysis showed that the type of surgery significantly moderated OS and DFS, while total downstaging and pN were predictive for DFS only. For treatment per protocol 5-year OS, DFS and LC were 80.9% (95% confidence interval [CI] 69.7-92.1), 77.1% (95% CI 65.1-89.1) and 95.2% (95% CI 88.7-100), respectively. The proportion of patients with severe late (CTCAE G ≥ 3) gastrointestinal, urinary and sexual toxicity was 15%, 2% and 8% respectively, with one reported secondary carcinoma. CONCLUSIONS: Preoperative IMRT-SIB without dose escalation was well tolerated, with a low acute toxicity profile, we achieved a high rate of pCR and showed encouraging 5-year OS, DFS and LC.

Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy - single institute experience.

BACKGROUND: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine. PATIENTS AND METHODS: We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients. RESULTS: Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12-99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5-12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2-80.8%) and 45.8% (95% CI: 32.7-58.9%). With the median follow-up time of 23 months (range 2-35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5-93.9%) and 68.6% (95% CI: 57.2-79.9%). CONCLUSIONS: Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.

Six-Minute Walk Distance in Breast Cancer Survivors-A Systematic Review with Meta-Analysis.

The six-minute walk test (6MWT) is a widely used test for the indirect measurement of cardiorespiratory fitness in various cancer populations. Although the 6MWT is a simple test, there are no normative values for breast cancer survivors (BCS) or comparisons of results with healthy counterparts. A systematic review with a meta-analysis was carried out, which included studies from 2007 to 2020. Ninety-one studies were found, 21 of which were included in the quantitative synthesis. Among them were 9 randomized controlled trials (RCT), 8 prospective cohort studies and 4 cross-sectional studies. A total of 1084 BCS were included. Our results revealed that healthy subjects (n = 878) covered a significantly greater distance than BCS during the 6MWT (589.9 m vs. 477.4 m, p < 0.001), and the results of the meta-regression analysis showed that the 6MWD was predicted by the participants' BMI (p < 0.001), but not by their age (p = 0.070). After adjustment for BMI, the healthy subjects also covered greater distances than the BCS (103 m; p < 0.001). The normative values of 6MWT were presented for BCS. Besides, 6MWT distances distinguish between their healthy counterparts, therefore, the 6MWT distance is a relevant parameter for the assessment and monitoring of cardiorespiratory fitness in medical and exercise interventions for BCS.

Consolidation radiotherapy for patients with extended disease small cell lung cancer in a single tertiary institution: impact of dose and perspectives in the era of immunotherapy.

Background Consolidation radiotherapy (cRT) in extended disease small cell lung cancer (ED-SCLC) showed improved 2-year overall survival in patients who responded to chemotherapy (ChT) in CREST trial, however results of two meta - analysis were contradictive. Recently, immunotherapy was introduced to the treatment of ED-SCLC, making the role of cRT even more unclear. The aim of our study was to access if consolidation thoracic irradiation improves survival of ED-SCLC patients treated in a routine clinical practice and to study the impact of cRT dose on survival. We also discuss the future role of cRT in the era of immunotherapy. Patients and methods We retrospectively reviewed 704 consecutive medical records of patients with small cell lung cancer treated at the Institute of Oncology Ljubljana from January 2010 to December 2014 with median follow up of 65 months. We analyzed median overall survival (mOS) of patients with ED-SCLC treated with ChT only and those treated with ChT and cRT. We also compared mOS of patients treated with different consolidation doses and performed univariate and multivariate analysis of prognostic factors. Results Out of 412 patients with ED-SCLC, ChT with cRT was delivered to 74 patients and ChT only to 113 patients. Patients with cRT had significantly longer mOS compared to patients with ChT only, 11.1 months (CI 10.1-12.0) vs. 7.6 months (CI 6.9-8.5, p < 0.001) and longer 1-year OS (44% vs. 23%, p = 0.0025), while the difference in 2-year OS was not significantly different (10% vs. 5%, p = 0.19). The cRT dose was not uniform. Higher dose with 45 Gy (in 18 fractions) resulted in better mOS compared to lower doses 30-36 Gy (in 10-12 fractions), 17.2 months vs. 10.3 months (p = 0.03) and statistically significant difference was also seen for 1-year OS (68% vs. 30%, p = 0.01) but non significant for 2-year OS (18% vs. 5%, p = 0.11). Conclusions Consolidation RT improved mOS and 1-year OS in ED-SCLC as compared to ChT alone. Higher dose of cRT resulted in better mOS and 1-year OS compared to lower dose. Consolidation RT, higher number of ChT cycles and prophylactic cranial irradiation (PCI) were independent prognostic factors for better survival in our analysis. For patients who received cRT, only higher doses and PCI had impact on survival regardless of number of ChT cycles received. Role of cRT in the era of immunotherapy is unknown and should be exploited in further trials.

Precision Radiation Therapy for Metastatic Spinal Cord Compression: Final Results of the PRE-MODE Trial.

OBJECTIVE: To investigate precision radiation therapy for metastatic spinal cord compression and compare it to conventional radiation therapy. METHODS AND MATERIALS: In a multicenter phase 2 study, 40 patients received 5 Gy × 5 fractions of precision radiation therapy (38 volume modulated arc therapy, 2 intensity modulated radiation therapy) for metastatic spinal cord compression and were evaluated for local progression-free survival (LPFS), motor function, ambulatory status, sensory function, sphincter dysfunction, pain, distress, overall survival (OS), and toxicity. Maximum spinal cord dose was 101.5% (myelopathy risk, <0.03%) of the prescription dose. Patients were compared with a historical control group conventionally irradiated with 4 Gy × 5 fractions (propensity score analysis). The equivalent dose in 2 Gy-fractions of 5 Gy × 5 fractions is similar to 3 Gy × 10 fractions, which results in better LPFS than 4 Gy × 5 fractions. It was assumed that 5 Gy × 5 fractions is also superior to 4 Gy × 5 fractions for LPFS. (ClinicalTrials.gov-identifier: NCT03070431) RESULTS: Six-month rates of LPFS and OS were 95.0% and 42.6%, respectively. Improvement of motor function occurred in 24 patients (60%). Thirty-three patients (82.5%) were ambulatory after radiation therapy. Eight of 16 patients (50.0%) with sensory deficits improved. Pain and distress relief were reported by 61.9% and 54.2% of patients 1 month after radiation therapy. Grade 3 toxicities occurred in 1 patient and grade 2 toxicities in another 3 patients. Of the control group, 664 patients qualified for the propensity score analysis; 5 Gy × 5 fractions was significantly superior to 4 Gy × 5 fractions with regard to LPFS (P = .026) but not motor function (P = .51) or OS (P = .82). CONCLUSIONS: Precision radiation therapy with 5 Gy × 5 fractions was well tolerated and effective and appeared superior to 4 Gy × 5 fractions in terms of LPFS. The retrospective nature of the historic control group, which might have led to a hidden selection bias, needs to be considered when interpreting the results.

Definitive radiochemotherapy in esophageal cancer - a single institution experience.

Background Definitive radiochemotherapy is the preferred treatment option in patients with the cancer of the cervical esophagus and a viable treatment option in patients with the cancer of lower two thirds of the esophagus, who decline proposed surgical treatment. The purpose of the study was to evaluate the treatment results with definitive radiochemotherapy of patients with esophageal cancer, treated in a single institution in the period from 2010 to 2017. Patients and methods All available medical data for 55 patients with esophageal cancer, who were treated with definitive radiochemotherapy with curative intent, were analyzed retrospectively. Patients were irradiated to a total dose to the tumor of 70 Gy (2 Gy per fraction) in upper third (cervical) tumors or to the mean total dose of 57.6 Gy (1.8 Gy per fraction) in middle third (intrathoracic) tumors. All but one patient received concomitant chemotherapy, with the majority of them (41 patients; 74.5%) receiving concomitant chemotherapy with 5-fluorouracil in continuous 96 hours infusion and cisplatin. The main endpoints of the study were overall survival (OS; death of any cause), locoregional control (LRC; local and/or regional disease recurrence) and disease-free survival (DFS; recurrence of any kind and/or new primary malignoma). Univariate analysis testing the impact of different parameters on survivals and analysis of treatment related side effects were performed as well. Results The mean age of patients was 62 years (SD 9 years; range: 29-80 years). Majority of them had squamous cell cancer (53 patients; 96.4%) in the stage T3 or T4 (47 patients; 85.5%) and/or N+ disease (35 patients; 63.6%). Median follow-up time for the whole group of patients was 16.8 months (range: 0.3-81.8 months). At the time of analysis 14 (25.5%) patients were still alive. Rates for OS, LRC and DFS at two and five years were as follows: 47% and 19.4%; 43.7% and 41%; 32.1% and 11.5%, respectively. Conclusions The study results of treatment with definitive radiochemotherapy in patients with esophageal cancer are similar to the results of other studies. Majority of patients ended the treatment according to the protocol, which at least in part can be attributed to the adequate and well organized supportive treatment in our institution.

Overstaged Rectal Cancer by MRI due to Fibrosis Induced by Tattoo Marker.

Endoscopic colorectal tattooing with carbon-based dyes is commonly employed in order to assist with later localization of the lesion. Although carbon is thought to be nontoxic, there usually is some inflammatory reaction with fibrosis and granuloma formation after tissue injection. The aim of this report is to alert to a possible underestimated, late consequence of colorectal carbon-based marker tattooing, namely pronounced fibrosis at the site of the injection that could lead to a blurring and misinterpretation of changes evaluated by radiological techniques. We describe a case of cT stage overestimation due to fibrosis of the rectal wall and perirectal fat, induced by carbon-based dye injection in a 66-year-old patient. In our case it was an overestimation of MR evaluation in the case of early invasive carcinoma. Although there have been some studies on tissue effect of carbon-based dyes, the possible scenario consequence of cancer stage overestimation due to fibrosis has not yet been described. Such a mistake could lead to inappropriate overtreatment. Clinicians must be aware of the possible consequences of dye injection and resultant overestimation of T stage of colorectal cancer. More histological studies concerning histological changes after carbon-based marker tattooing are needed to establish the extent of its significance.

Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01 Trial.

Background The purpose of the study was to improve treatment efficacy for locally advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy preoperatively to one induction and two consolidation cycles. Patients and methods Between October 2011 and April 2013, 66 patients with LARC were treated with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction. The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and 1250mg/m2/12h, respectively. The primary endpoint was pathologic complete response (pCR). Results Forty-three (65.1%) patients were treated according to protocol. The compliance rates for induction, consolidation, and adjuvant chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by 65/66 patients, with G ≥ 3 non-hematologic toxicity at 13.6%. The rate of pCR (17.5%) was not increased, but N and the total-down staging rates were 77.7% and 79.3%, respectively. In a median follow-up of 55 months, we recorded one local relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 64.0% (95% CI 63.89-64.11) and 69.5% (95% CI 69.39-69.61), respectively. Conclusions In LARC preoperative treatment intensification with capecitabine before and after radiotherapy is well tolerated, with a high compliance rate and acceptable toxicity. Though it does not improve the local effect, it achieves a high LR rate, DFS, and OS.

Preoperative Intensity-modulated Chemoradiation Therapy with Simultaneous Integrated Boost in Rectal Cancer: 2-year Follow-up Results of Phase II Study.

BACKGROUND: The aim of the study was to investigate the feasibility and safety of experimental fractionation using intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) to shorten the overall treatment time without dose escalation in preoperative radiochemotherapy of locally advanced rectal cancer. PATIENTS AND METHODS: Between January 2014 and November 2015, a total of 51 patients with operable stage II-III rectal adenocarcinoma were treated. The preoperative treatment with intensity modulated radiation therapy (IMRT) and a pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumour in 22 fractions, with standard concomitant capecitabine, was completed in 50 patients out of whom 47 were operated. The median follow-up was 35 months. RESULTS: The rate of acute toxicity G ≥ 3 was 2.4%. The total downstaging rate was 89% and radical resection was achieved in 98% of patients. Pathologic complete response (pCR) was observed in 25.5% of patients, with 2-year local control (LC), disease free survival (DFS), and overall survival (OS) of 100% for this patient group. An intention-to-treat analysis revealed pN to be a significant prognostic factor for DFS and OS (P = 0.005 and 0.030, respectively). LC for the entire group was 100%, and 2-year DFS and OS were 90% (95 % CI 98.4-81.6) and 92.2% (95% CI 99.6-84.7), respectively. CONCLUSIONS: The experimental regime in this study resulted in a high rate of pCR with a low acute toxicity profile. Excellent early results translated into encouraging 2-year LC, DFS, and OS.

Health-related Quality of Life Assessed by the EORTC QLQ-C30 Questionnaire in the General Slovenian Population.

BACKGROUND: The aim of our study was to obtain reference data of the EORTC QLQ-C30 quality of life dimensions for the general Slovenian population. We intend to provide the researchers and clinicians in our country with the expected mean health-related quality of life (HRQL) scores for distinctive socio-demographic population groups. METHODS: The EORTC QLQ-C30 questionnaire supplemented by a socio-demographic inquiry was mailed or distributed to 1,685 randomly selected individuals in the Slovenian population aged 18 - 90. Answers from 1,231 subjects representing socio-demographic diversity of the Slovenian population were collected and transformed into EORTC dimensions and symptoms. The impact of socio-demographic features on HRQL scores was assessed by multiple linear regression models. RESULTS: Gender, age and self-rated social class are the important confounders in the quality of life scores in our population. Men reported better quality of life on the majority of the specific scales and, at the same time, reported fewer symptoms. There was no gender-specific difference in cognitive functioning. The mean scores were consistently lower with age in both sexes. CONCLUSIONS: This is the first study to report the normative EORTC QLQ-C30 scores for one of the south-eastern European populations. The reported expected mean scores allow Slovenian oncologists to estimate what the quality of life in cancer patients would be, had they not been ill. As they are derived by common methodology, our results can easily be included in any further international comparisons or in the calculation of European summarized HRQL scores.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial.

BACKGROUND AND PURPOSE: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. METHODS AND MATERIALS: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m2/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). RESULTS: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. CONCLUSIONS: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

Mucosal melanoma of the head and neck: a population-based study from Slovenia, 1985-2013.

OBJECTIVES: To assess the incidence and to review experience with the treatment of mucosal melanoma of the head and neck (MMHN) in Slovenia between 1985 and 2013. METHODS: The National Cancer Registry database and clinical records with outcome data of identified patients treated during the period 1985-2013 in Slovenia were reviewed. RESULTS: In a 29-year period, 61 patients with MMHN were identified, representing 0.5 % of all head and neck malignant tumors and 42 % of all mucosal melanomas in Slovenia. 72 % originated in the sinonasal tract and were predominantly (78 %) diagnosed as a local disease. Regional metastases at diagnosis were more frequent in patients with oral/oropharyngeal primary (44 %; sinonasal MMHN 11 %, p = 0.006). Curative intent treatment was given to 48 (79 %) patients. The overall survival (OS) rates at 2 and 5 years for the whole cohort were 43 % and 18 %, respectively, and for the curative intent group 53 % and 24 %, respectively. In the latter group, multivariate analyses showed postoperative radiotherapy (PORT) to be predictive for locoregional control (LRC) (hazard ratios [HR] for surgery with PORT vs. surgery alone: 1.0 vs. 3.9, p = 0.037), whereas only the World Health Organization performance status (HR for grade 0 vs. grade 1 vs. grade >1: 1.0 (p = 0.022) vs. 1.2 (p = 0.640) vs. 7.7 (p = 0.008)) significantly influenced OS. CONCLUSIONS: MMHN is a rare tumor with a poor prognosis. Combination of surgery and PORT offers the best prospects for LRC but without improvement of OS. Due to potential toxicity of high-dose RT such treatment is indicated in patients in whom LRC outweighs the risks of serious adverse effects.

Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer.

BACKGROUND: To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. PATIENTS AND METHODS: Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. RESULTS: Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, disease-free survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. CONCLUSIONS: Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patients' cure.

Radiotherapy for inverted papilloma: a case report and review of the literature.

BACKGROUND: Sinonasal inverted papilloma (IP) is a rare, usually benign tumor arising from the respiratory mucosa of the sinonasal tract. Surgical resection is the treatment of choice. In histologically overt benign IPs (i.e. without associated malignancy) irradiation was employed only anecdotally. The patient with gross residual of benign IP after up-front surgery that was subsequently treated with irradiation is presented and the literature reports on the use of radiotherapy (RT) in this tumor type are reviewed. CASE REPORT: After the surgical treatment the residuum in the region of the sphenoid and adjacent cavernous sinus was irradiated to 54 Gy in 1.8 Gy daily fractions. No recurrence or deterioration of olfaction, hearing or vision was observed 2.6 years post-RT. REVIEW OF THE LITERATURE: In the literature, six reports were identified with 16 patients describing necessary details on RT and outcome. Twelve of 14 cases (our case included) with gross or subtotal tumor resection and postoperative RT were locally controlled. The lowest and the median irradiation doses were 47.15 Gy and 56.5 Gy, respectively, and the follow-up period ranged between 0.5-20.5 years (median 7.8 years). CONCLUSIONS: RT is safe and valuable treatment option in histologically overt benign IPs. It is indicated when the risk of tumor recurrence after surgery is increased and in inoperable tumors.

Sinonasal inverted papilloma associated with squamous cell carcinoma.

BACKGROUND: The aims of the study were to review single-institution experiences with sinonasal inverted papilloma associated with squamous cell carcinoma (IP/SCC), to analyze the presence of human papillomavirus (HPV) and to evaluate the role of radiotherapy. PATIENTS AND METHODS: Five patients with IP/SCC were identified in the prospective institutional databases (1995-2005) and HPV status was determined in all five tumors. RESULTS: Four out of five patients had T3-4 tumors; no nodal involvement was seen in any of them. Four patients had curative surgery, supplemented in three of them with radiotherapy. Debulking surgery was performed in the patient with a non-resectable tumor followed by radical radiotherapy. Tumor was controlled locally in three patients at 8, 46 and 58 months post-surgery. Local failure occurred in two patients: after endoscopic resection of a T1 tumor (the recurrent tumor was successfully salvaged with additional surgery) and in a patient with an inoperable tumor. No regional or distant metastases occurred. HPV status was determined in all five tumors and three of them were found positive for HPV type 11. CONCLUSIONS: In operable sinonasal IP/SCC, upfront surgery and postoperative radiotherapy to the tumor bed with dose levels comparable to those used for invasive SCC are recommended. For non-resectable disease, radical radiotherapy to a dose of 66-70 Gy could be of benefit.

The role of radiation therapy in locally advanced breast cancer.

The purpose of the study was to evaluate and compare the impact of postoperative radiotherapy, whether it was based on the clinical stage at presentation of the disease or on the pathological downstaged disease after initial chemotherapy for non-inflammatory locally advanced breast cancer (LABC). We retrospectively analyzed locoregional recurrence (LRR), relapse free survival (RFS), overall survival (OS) and disease free survival (DFS) in 55 patients treated for non-inflammatory LABC with neoadjuvant chemotherapy and surgery with or without radiotherapy. The mean follow-up was 55 months. The 3-year OS was 74%, DFS 73% and RFS 87%. The OS and DFS benefit was seen in those receiving radiation, with a mean OS of 89 months versus 68 months (p = 0.029) and mean DFS of 72 months versus 54 months (p = 0.029). Total LRR was 11% (8% versus 17% in the non-radiotherapy group, p = 0.349) and mean RFS of 95 months versus 86 months (p = 0.164). If the treatment planning was to be based on the original extent of the disease, then all patients in our study should have received adjuvant radiotherapy. Significantly lower OS and DFS without the addition of radiotherapy suggests that indication for radiation treatment should be based on the clinical pre-chemotherapy stage rather than the pathological post-chemotherapy stage. Radiation should therefore always be considered regardless of the response to initial chemotherapy for non-inflammatory LABC.