BackgroundMost patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2.MethodsPatients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients’ CD14+ monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1.ResultsBetween November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events).ConclusionsDCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC.Trial registration numberNCT02107937, EudraCT2010-021462-30.

Randomized trial of DCVAC/OvCa, dendritic cell-based immunotherapy in platinum-sensitive ovarian cancer.• The addition of DCVAC/OvCa to second-line chemotherapy had a favorable safety profile.• DCVAC/OvCa did not improve progression-free survival, but did prolong overall survival by 13.4 months.• DVCAC/OvCa plus chemotherapy enhanced surrogate T-cell activity.

Modern therapeutic management of patients with cancer is associated with many adverse side effects, including fatigue defined as weariness, burnout, lassitude, malaise, apathy, impatience, and/or inability to perform daily activities. It occurs frequently before the diagnosis of cancer and may persist for a long time after the end of cancer therapy. It is a common problem that occurs regardless of the type of cancer and applied therapeutic procedure. The appearance of this symptom significantly affects the quality of life of patients and often reduces the effectiveness of implemented treatment. The symptom of fatigue occurs among approximately 80% of patients treated with chemotherapy and/or radiotherapy, as well as among more than 75% of patients with metastatic disease. Causes of fatigue include metabolic and immune system disorders as well as increased level of tumour necrosis factor α (TNF-α). Recent studies also indicate a significant contribution of other cytokines, especially pro-inflammatory ones, i.e. interleukin-1 (IL-1), interleukin-6 (IL-6), soluble tumour necrosis factor receptor type II (sTNF type II) and C-reactive protein (CRP). A patient reporting fatigue should be properly diagnosed and thoroughly interviewed by doctors. Patients are mostly treated non-pharmacologically (by means of physical exercise and psychotherapy) and pharmacologically (by applying methylphenidate and methylprednisolone). What is also extremely important is proper education of the patient and their closest family/friends on the symptoms, which significantly reduces anxiety and stress. On the other hand therapeutic management hinders the subjectivity of feeling and lack of standardised scales to rate symptoms.

Background: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. Methods: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3–49 months). Results: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). Conclusions: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment.

The aim of the present study was to evaluate the efficacy, safety and tolerability of local treatment of liver metastases of various types of cancer using brachytherapy with computed tomography (CT) imaging. Retrospective analysis of 61 patients with unresectable hepatic metastases treated with CT-guided interstitial high dose rate (HDR) brachytherapy of the liver between April 2014 and December 2016 was performed. Patients were treated with a single fractional dose of 15-25 Gy. Statistical analysis was performed on local relapse free survival (LRFS), progression free survival (PFS) and overall survival (OS) rates across the group. In the 6 and 12-month follow-up periods, the 6- and 12-month LRFS rates were 88.7 and 70.7%, PFS rates were 78.1 and 53.8% and the OS rates were 96.7 and 79.6%, respectively. In the Cox regression analysis, the 100% isodose was a statistically significant predictor of LRFS (P=0.01) and PFS (P=0.02), but it was not significant in OS (P=0.07). The 90% isodose was a statistically significant predictor of LRFS (P=0,03) but not significant in PFS (P=0.17) or OS (P=0.25). In all patients, no serious complications were observed. Overall, 30% of patients experienced pain at the injection site, and 50% exhibited nausea or vomiting. In 2 patients, minor subcapsular bleeding occurred without clinical significance, and 1 patient was diagnosed with a pneumothorax that was not clinically significant. Brachytherapy HDR with CT imaging is an effective and safe method of local treatment of liver metastases. The effectiveness of the treatment is probably dose-dependent, and increases with increasing dosage.

PurposeThe aim of the study was the evaluation of image guided transdermal application of interstitial brachytherapy in patients undergoing repeated irradiation for relapsed local tumor of the head and neck area.Material and methodsThe article describes transdermal application of interstitial high-dose-rate (HDR) brachytherapy in 4 patients treated due to relapsed local tumor in soft palate, submandibular area, laryngopharynx, as well as pterygoid muscles and maxillary sinus. The application was conducted under continuous computed tomography (CT)-image guidance (CT fluoroscopy). Patients qualified for this type of treatment had neoplastic lesions located deep under the skin surface. Because of their location, access to the lesions was limited, and the risk of damaging the adjacent tissues such as vessels and nerves was high. The following parameters have been evaluated: clinical response using RECIST 1.1, incidence of perisurgical complications using CTCAE 4.0 and the frequency of occurrence of radiotherapy related early morbidity using RTOG.ResultsVarious radiation schemes were used, from 3 to 5 fractions of 3.5-5 Gy. The median total dose (D90) was 20.6 Gy. Biologic effective dose (BED) and equivalent 2 Gy (DEQ2) median doses were 30.4 Gy and 25.3 Gy, respectively. In the follow-up period of 3-7 months (the median value of 3.5 months), 2 patients had partial regression of the disease and in 2 others the neoplastic process was stabilized. None of the patients had serious complications of treatment (of 3rd degree or higher).ConclusionsComputed tomography-image guided brachytherapy proved to be a safe method of treatment in patients with local relapse in sites, in which traditional visually controlled application was impossible due to risk of complications. Despite short observation period and small study group, it seems justified to conduct prospective studies for the evaluation of efficacy and safety of CT-image guided brachytherapy.

The aim of this study was to determine the role of adjuvant endovaginal brachytherapy HDR (High Dose Rate) or observation, as well as identification of risk factors of tumor recurrence. The study included 178 women after radical hysterectomy. All patients belonged to the group of low- and medium-risk stage I FIGO. Analysis consisted of 3-, 5-, and 10-year OS, DFS, and LRFS in both groups. Follow-up was more than 6.5 years. The 5-OS, 5-DFS, and 5-LRFS were 93%, 96%, and 98% in the treated group and 95%, 94%, and 96% in the observed group, respectively. These differences were not statistically significant. There was a statistically significant difference in 5-OS in the treated group, between low- and medium-risk subgroups (100% versus 87.55%, p = 0.018). There was a better prognosis among the patients with FIGO IA compared to FIGO IB (5-DFS, 97 versus 86%, p = 0.047). Among the risk factors, there were only statistically significant differences in the 5-OS, between the ages of ≤ 70 years and >70 years. Use of brachytherapy may affect the reduction in the number of local recurrences at the vaginal stump (6% versus 2%). This is particularly noticeable in the low-risk subgroup (9% versus 0%).

5521 Background: Most patients with EOC relapse despite PDS and CMT. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to CMT stimulates antitumor immunity and improves clinical outcomes. Methods: Key eligibility criteria were FIGO stage III EOC (serous, endometrioid, or mucinous), post-PDS with < 1 cm maximal residuum, no prior systemic therapy, and ECOG 0-2. In part 1, patients were randomized up to 6 weeks after PDS, 1:1:1, into arm A (A; DCVAC concomitant with CMT), arm B (B; DCVAC sequential after CMT), and arm C (C; CMT). Patients were stratified by tumor residuum (0 or < 1 cm). CMT consisted of 6 cycles of carboplatin (AUC 5-7) and paclitaxel (175 mg/m2). Patients in A and B received up to 10 doses of DCVAC (1×107 DCs/dose). The primary endpoint was radiologically assessed progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Results presented refer to a protocol-defined modified intention-to-treat population (mITT) including patients who received ≥1 CMT dose in C or ≥1 DCVAC dose in A and B. Results: Between November 2013 and March 2016, 99 patients were randomized. At the final analysis, the mITT included 31 patients in A, 29 patients in B, and 30 patients in C. Key baseline characteristics and DCVAC exposure were comparable across treatment arms. Median PFS was 20.3 months in A, not reached in B, and 21.4 months in C, with corresponding HRs (95% CI) compared to C of 0.98 (0.48-2.00) in A and 0.39 (0.16-0.96) in B. The PFS benefit in B was statistically significant (p = 0.034) This was supported by a non-significant trend in OS in A and B. Median OS was not reached in any arm at the time of median follow-up of 66 months (34% of events). Patients with low CD8+ T-cell counts (CD8Lo) in tumor samples in A and B had significantly improved clinical outcomes compared to patients in C with CD8Lo: median PFS gain of 6 months (19 vs 13 months) and a more robust OS gain (median not reached vs 31 months), with minimal difference between A and B. This effect could not be attributed to statistical differences in high CD8+ T-cell counts (CD8Hi) density patients. These findings indicated the best clinical outcome in DCVAC patients with immunologically “cold” tumors in both DCVAC arms. DCVAC showed a good safety profile with only 8 DCVAC-related adverse events (Grade 1-2). Conclusions: DCVAC improved PFS and OS outcomes in patients with newly diagnosed EOC, predominantly in patients with immunologically “cold” tumors, thus representing a promising treatment option in this patient population. Clinical trial information: NCT02107937.