Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.

Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1).

BACKGROUND: There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting. PATIENTS AND METHODS: Patients with aUC a creatinine clearance (CrCl) of <60 but ≥30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1). They received vinflunine 250 or 280 mg/m(2) (based on baseline CrCl) on day 1, plus either gemcitabine [750 mg/m(2) escalated to 1000 mg/m(2) in cycle 2 if no toxicity grade (G) ≥2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days]. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (α = 5%, ß = 20%). RESULTS: Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non-haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively. CONCLUSION: Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study. CLINICALTRIALS.GOV PROTOCOL IDENTIFIER: NCT 01599013.

Parallel-opposed fields versus four fields, and two- versus three-dimensional radiotherapy planning in thin patients with gynecological malignancies.

Conformal radiotherapy constitutes the standard management of pelvic malignancies, yet its role in thin patients remains debatable. This study compares dose distribution for 2D and 3D treatment techniques for cobalt (60Co) and high energy photons from linear accelerator (LA) in cervical and endometrial cancer patients with antero-posterior diameter of less than 20 cm. CT-based 3D treatment planning and 2D simulation were performed in 10 patients. Particular techniques were compared in terms of treatment portal areas, coverage of planning target volume (PTV) and sparing of critical organs. For 60Co beams, PTV was not covered adequately with 2D fields in nine patients and with conformal fields in seven. For LA, PTV was not adequately covered with 2D two-field and 2D four-field ("box") technique in three and one patients, respectively. Mean bladder dose was comparable for all plans. Both 2D "box" and 3D "box" technique spared additional portion of the rectum volume included in 95% isodose, compared to two-field plan. 3D treatment planning better protected the small intestine. Use of multiple field techniques and 3D planning allows for some improvement of PTV coverage and normal tissue sparing, although the magnitude of this benefit must be weighted against savings of time and labour related to use of simpler treatment techniques.

Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial.

BACKGROUND: Trastuzumab (Herceptin(R)) improves disease-free survival (DFS) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess the magnitude of its clinical benefit for subpopulations defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant (HERA) study. PATIENTS AND METHODS: HERA is an international multicenter randomized trial comparing 1 or 2 years of trastuzumab treatment with observation after standard chemotherapy in women with HER2-positive breast cancer. In total, 1703 women randomized to 1-year trastuzumab and 1698 women randomized to observation were included in these analyses. Median follow-up was 23.5 months. The primary endpoint was DFS. RESULTS: The overall hazard ratio (HR) for trastuzumab versus observation was 0.64 [95% confidence interval (CI) 0.54-0.76; P < 0.0001], ranging from 0.46 to 0.82 for subgroups. Estimated improvement in 3-year DFS in subgroups ranged from +11.3% to +0.6%. Patients with the best prognosis (those with node-negative disease and tumors 1.1-2.0 cm) had benefit similar to the overall cohort (HR 0.53, 95% CI 0.26-1.07; 3-year DFS improvement +4.6%, 95% CI -4.0% to 13.2%). CONCLUSIONS: Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status, even those at relatively low risk for relapse.

Complications of breast-cancer radiotherapy.

Although the beneficial effect of postoperative radiotherapy for breast cancer is well documented, this treatment may be related to a number of complications, which may affect patient quality of life and possibly survival. Among significant long-term irradiation sequelae are cardiac and lung damage, lymphoedema, brachial plexopathy, impaired shoulder mobility and second malignancies. The risk of these complications, particularly high with old, suboptimal irradiation techniques, has decreased with the introduction of modern technologies. In this paper, we review the contemporary knowledge on the toxicity of breast-cancer radiotherapy and discuss possible preventive measures.

A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC).

A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47-81 years (mean 66), performance status 1-4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC.

[Results of surgical treatment of vulvar cancer]. / Wstepna ocena wyników operacyjnego leczenia raka sromu.

OBJECTIVES: Vulvar cancer is a relatively rare genital malignancy. The mainstay of it's treatment is surgery. DESIGN: A retrospective study of vulvar cancer patients treated between 1967 and 1995 at Department of Gynaecology, Medical University of Gdansk. MATERIALS AND METHODS: The type and outcome of surgical treatment was studied in 162 consecutive patients. RESULTS: The surgery was limited to the vulva in 24% cases and in the reaming 76% of patients removed were also regional lymph nodes. Median survived of the whole group was 105 months and actuarial 5-year survival-60%. CONCLUSIONS: The results of treatment of vulvar cancer in presented series correspond well with the literature data.

Influence of brachytherapy applicators geometry on dose distribution in cervical cancer.

AIM: Although the relationship between the dose delivered to adjacent organs (urinary bladder and rectum) and the frequency and severity of treatment complications has been reported in many series, the factors influencing pelvic dose distribution are not well defined. The aim of the study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and the impact of various therapy-dependent factors on patient anatomy and on dose distribution in particular applications. PATIENTS AND METHOD: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analysed factors included preceding external beam radiotherapy (EBRT) or brachytherapy applications, use of general anaesthesia for application and the system of pellet loading. RESULTS: Significant correlation was found between the size of applicators and doses to bladder, rectum and points B: larger vaginal applicators produced lower dose in bladder and rectum and higher dose in point B (all p < 0.0001), longer uterine tandems produced lower dose in rectum and higher dose in point B (both p < 0.0001). Significant decrease in the frequency of use of large applicators (ovoids: p < 0.0001, tandems: p = 0.055) and worsening of dose distribution, i.e. higher doses to critical organs (respectively: bladder p = 0.0012, rectum p = 0.02) and lower point B dose (p = 0.0001) were observed at consecutive brachytherapy applications. Similar situation occurred in patients, who received EBRT prior to brachytherapy (ovoids: p < 0.001, tandem: p = 0.04, bladder dose: p = 0.009, rectal dose: p = 0.073, point B dose: p = 0.059). Vaginal applicators were larger (p = 0.026) and the dose distribution was better (bladder: p = 0.023, rectum: p = 0.002, point B: p = 0.0001) in patients who had their insertions performed under general anaesthesia. The comparison of 2 consecutively used systems of pellet loading revealed more favourable dose distribution: lower dose for bladder (p = 0.014) and higher dose for point B (p < 0.0001) for the system, which utilised more sources in ovoids and in the distal part of the uterine tandem, in spite of more frequent use of smaller applicators in this group of patients. In multivariate analysis ovoid size was related to preceding external beam radiotherapy (p = 0.025). Uterine tandem length was dependent on the number of preceding intracavitary applications (p < 0.001) and preceding external beam radiotherapy (p = 0.007). Bladder dose was related to preceding brachytherapy (p = 0.011) and the pattern of pellet loading (p = 0.031). Rectal dose was dependent only on the use of general anaesthesia during application (p = 0.001) and point B dose was dependent on the pattern of pellet loading (p < 0.001) and marginally-on the use of preceding external beam radiotherapy (p = 0.06). CONCLUSIONS: The results of this study allow for identification of treatment-related factors determining pelvic dose distribution in cervical cancer brachytherapy and may potentially enable optimisation of this distribution in particular clinical situation.

Patient-related factors determining geometry of intracavitary applicators and pelvic dose distribution during cervical cancer brachytherapy.

PURPOSE: The aim of this study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and to analyze the impact of various patient- and disease-related factors on applicators' geometry and on dose distribution in particular applications. METHODS AND MATERIALS: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analyzed factors included patient age, weight, number of vaginal deliveries, and disease stage. RESULTS: The use of larger vaginal applicators resulted in lower bladder and rectum doses and in higher point B doses (all p < 0.0001); longer uterine tandems produced lower rectum doses and higher point B doses (both p < 0.0001). Increasing patient age and disease stage resulted in a decreased frequency of use of large ovoids (both p < 0.0001) and of long tandems (age: p = 0.0069, stage: p = 0.004). As a result, higher doses to bladder (age: p < 0.0001, stage: p = 0.017) and rectum (age: p = 0.037, stage: p = 0.011) were observed. Increasing age also resulted in lower point B doses (p < 0.0001). Increasing patient weight correlated with less frequent use of long tandems (p = 0.0015) and with higher bladder doses (p = 0.04). Higher number of vaginal deliveries was related to the increase in the use of long tandems (p = 0.002); in patients who had had at least one vaginal delivery, point B doses were significantly higher (p = 0.0059). In multivariate analysis ovoid size and uterine tandem length were dependent on patient age (respectively: p < 0.001 and p = 0.001), disease stage (respectively: p = 0.003 and p = 0.008) and on the number of vaginal deliveries (respectively: p = 0.07 and p = 0.008). Doses to critical organs and to points B were dependent on patient age (respectively: p < 0.001, p = 0.011, and p < 0.001) and on disease stage (respectively: p < 0.001, p = 0.004, and p = 0.048). CONCLUSION: The results of this study allow for identification of some patient- and disease-related factors influencing pelvic dose distribution in cervical cancer brachytherapy. This potentially may enable optimization of the dose distribution in particular clinical situations.

[Small cell tumor of the uterine neck]. / Drobnokomórkowy rak szyjki macicy.

Small cell cervical cancer is a rare, but important for its distinct biological properties and clinical behaviour, neoplasm. It is both morphologically, and clinically aggressive, in many aspects resembling small cell lung cancer. This paper discusses the present knowledge about biology and treatment of this rare malignancy.

[Alveolar rhabdomyosarcoma of the uterine cervix]. / Miesak Prazkowanokomórkowy pecherzykowy szyjki macicy.

A rare case of cervical alveolar rhabdomyosarcoma in a 45-year old female is presented. The removal of the tumour was performed in two stage-procedure, due to its large dimensions: first the bulk of the tumour was removed per vaginam, proceeding afterwards to a radical hysterectomy. Metastases were detected in pelvic lymph nodes. The patient was given postoperative radiotherapy, but a dissemination of the tumour was found at the termination of the treatment and the patent died 3.5 months after surgery.