Haematotoxicity in IMRT/VMAT curatively treated anal cancer.

INTRODUCTION: Curative chemoradiotherapy of squamous cell carcinoma achieves long-term complete remissions in most patients and minimizing treatment toxicity becomes crucial issue. The aim of the retrospective analysis was to determine an acceptable dose to the bone marrow for radiotherapy planning not leading to increased haematological toxicity. PATIENTS AND METHODS: In the period 2013-2019, 40 patients with squamous cell carcinoma were curatively treated at the Department of Oncology of the University Hospital Motol using intensity modulated radiotherapy (IMRT) /volumetric modulated arc radiotherapy (VMAT) technique. Women make up 90% of the group, the average age at the time of dia-gnosis was 65 years (47-81). Chemotherapy mitomycin C and 5-fluorouracil was given to 68% of patients. The bone marrow was contoured in the Varian Eclipse planning system, version 15.6. RESULTS: Acute hematotoxicity (G3, 4, 5 according to Common Terminology Criteria for Adverse Events - CTCAE) was significantly associated with the concomitant chemoradiotherapy (P = 0.002) and the average dose to the bone marrow 27 Gy (P = 0.011). Late haematological toxicity was mild (maximum grade 1), asymptomatic, and no dependence of late haematotoxicity on any risk factor (age, gender, WHO performance status, bone marrow dose, CHT, BMI, smoking, stage) was proved. The overall survival at 5 years was 100% in stage I, 83% in stage II, 61% in stage III and 0% in stage IV. Local control at 5 years is 100% in stage I, 92% in stage II, 87% in stage III and 0% in stage IV. Local recurrence developed in 5% of radically treated patients. Distant metastases occurred in 8% of radically treated patients. Local recurrences or metastases occurred only during the first 2 years after the treatment. CONCLUSION: Radical chemoradiotherapy in the treatment of squamous cell anal carcinoma is highly effective. IMRT/VMAT enabled to apply a sufficiently effective dose to the tumor and elective areas and reduced not only acute skin, GI and GU toxicity, but also acute haematological toxicity in cases with the dose Dmean to bone marrow lower than 27 Gy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical, papers.

Improved survival in patients with FDG-PET/CT-based radiotherapy treatment planning for squamous cell anal cancer.

The aim of this retrospective analysis was to evaluate the impact of FDG-PET/CT-based target volume definition on locoregional control and survival, compared to conventional CT-based target volume definition and dose prescription. One hundred and twenty-two patients with squamous cell anal cancer were treated with curative radiotherapy (RT) alone (27%) or with RT with concurrent chemotherapy (73%) and analyzed. Forty-six percent had the early disease (stage I+II) and 54% were stage III. FDG-PET/CT-based staging was performed in 21% of the patients. The mean follow-up time was 60 months. Other risk factors affecting survival were investigated. According to initial staging in both groups (FDG-PET/CT and conventional CT) were 10% of stage IV disease, and they were excluded from radical radiotherapy and treated with palliative intent. Ninety-two percent of the patients achieved complete remission. Significant favorable factors in univariate analysis associated with disease-free survival (DFS) were PET/CT staging, T1/2 and N0 stage, and clinical stage I and II. Locoregional control (LRC) correlated with the T1/2 stage and initial performance status (PS) 0. There were no significant factors affecting overall survival (neither in univariate nor multivariate analysis). In multivariate analysis, the factor associated with better DFS was PET/CT staging and for LRC, PS 0 and concomitant chemoradiation. Acute toxicity was increased in the concurrent chemo-radiotherapy group. Two-, five- and ten-year overall survival rates were 83%, 69%, and 60%; disease-free survival rates were 76%, 73%, 73%; local control rates were 91%, 90%, and 90% and colostomy-free survival was 89%, 86%, and 81%, respectively. PET/CT staging allowed targeted dose escalation to the primary tumor and nodal metastases while decreasing dose to uninvolved regions, resulting in significantly improved DFS without compromising locoregional control.

[Czech version of EORTC QLQ-CX24 questionnaire for patients with cervical cancer]. / Ceská verze dotazníku EORTC QLQ-CX24 pro pacientky s karcinomem delozního hrdla.

OBJECTIVE: Translation and validation of the EORTC QLQ-CX24 questionnaire on quality of life into the Czech language and literature. TYPE OF STUDY: Prospective study. SETTING: Dept. of Obstetrics and Gynaecology, 2nd Medical Faculty, Charles University and Faculty Hospital Motol, Prague. METHODS: In concordance with the EORTC guidelines a questionaire for patients with cervical cancer was translated and validated. A group of 14 women who underwent the treatment for cervical cancer filled in the questionaire. T-test was used for the evaluation of the patient's characteristics and the differences in quality of life. RESULTS: We present a Czech version of the questionaire EORTC QLQ-CX24 and the description how to evaulate it. In comparison of the two treatment groups no statistically significant differences have been found. CONCLUSION: EORTC QLQ-CX24 is an internationally accepted questionnaire focused on patients with cervical cancer which should be incorporated into the projects dealing with women undergoing treatment for this disease.

[Chemotherapy during pregnancy]. / Chemoterapie behem tehotenství.

OBJECTIVE: The aim of the study is to summarize current data on chemotherapy administered during pregnancy. TYPE OF STUDY: Review article. SETTING: Dept. of Obstetrics and Gynaecology of the Charles University in Prague, 2nd Medical Faculty, University Hospital. SUBJECT AND METHOD: Pubmed database was searched between the years 1980 and 2009 with the combinations of key words concerning cytostatics, therapy and pregnancy. Cisplatin administration was identified in 38 cases. Eight cases of administration of carboplatin during pregnancy were found with normal neonatal outcome Twenty-one case reports were found on the use of taxanes during pregnancy: 14 on paclitaxel and 7 on docetaxel. CONCLUSION: Based on the literature the administration of cytostatics during pregnancy can be considered under a close supervision and long-term follow-up in dedicated teams.

[The clinical significance of sentinel lymph node micrometastases in breast cancer]. / Klinický význam mikrometastáz karcinomu prsu v sentinelové uzline.

OBJECTIVE: The advent of sentinel lymph node biopsy and improvements in histopathological and immunohistochemical analysis has increased the rate at which micrometastases are identified. However their significance has been the subject of much debate. Published studies have reported divergent results regarding the significance and implications of axillary lymph node micrometastases. Some studies demonstrate no associations, whilst others have found these to be indicators of poor prognosis, associated with non-SLN involvement, in addition to local and distant failure. The objective of our study was to evaluate the impact of sentinel lymph node micrometastatic cancer to prognosis of the disease. DESIGN: Retrospective study. SETTING: Departments of Gynecology and Obstetrics, Faculty Hospital, Prague. METHODS: From January 2000 to December 2006 in 87 cases with sentinel axillary node negative cancer we reexamined the axillary tissue blocks by serial sectioning, haematoxilin-eosin staining and immunohistochemistry. Additional 15 cases of micrometastatic sentinel node involvement detected by frozen section were included. The overall and disease free survivals of patients with sentinel negative status (N0-67 cases) and with sentinel node micrometastases (Nmic-35 cases) were evaluated. The median follow-up was 60 months (24-96 months). RESULTS: Micrometastases (Nmic) were found in 20 cases (23%). From the group of 67 nodes negative patients (N0) in 7 cases (10.5%) developed tumor recurrence and from the group of 35 Nmic in 5 cases developed five tumor recurrences (13.3%). In the group of N0 patients developed 2 regional recurrences and 3 patients died, but 2 patients died of other causes. In the group of Nmic developed one regional recurrence and 3 patients died of generalization of disease. CONCLUSION: Our study demonstrated that the presence of sentinel node micrometastases is associated with risk of development of distant metastases and generalization of the disease, but not with higher risk of regional recurrence.

[Detection of postoperative lymphoedema in patients with breast cancer]. / Detekce pooperacního lymfedému u pacientek s karcinomem prsu.

OBJECTIVE: Lymphoedema is a severe postoperative complication after treatment of many malignancies. It is a pathological accumulation of extracellular water (ECW). Early diagnostic tool is needed. Multifrequency bioimpedance analysis (MFBIA) is a method for detection of changes in ECW. TYPE OF STUDY: Prospective study. SETTING: Dept. of Obstetrics and Gynaecology of the 2nd Medical Faculty, Charles University, Prague. METHODS: We measured a control group of 72 women and a group of 74 patients undergoing a breast cancer surgery during 18 month after the surgery by MFBIA and circumferency. Characteristics of the patients were recorded. The detection of lymphoedema was done using MFBIA, circumferency measurement and upon the symptoms of the patients. RESULTS: The average age in the controll and tested group was 40,1 and 58,9 years. The average size of the tumour, grade and positivity if oestrogen receptors was 15,1 mm, 2,04 and 43%. In 23 patients (21%) complete lymphadenectomy was performed, in 51 patients (79%) a detection of sentinel lymph node was performed. Lymphoedema was detected in 8 women (11%). In these patients MFBIA detected lymphoedema 9 month earlier in total than other methods. CONCLUSION: MFBIA is a low-cost and precise method for the detection od early stage postoperative lymphoedema. We recommend to incorporate MFBIA into standard dispensatory plan of every patient combined with circumferency measurement.

[A set of patients with breast cancer associated with pregnancy]. / Soubor pacientek s karcinomem prsu v souvislosti s tehotenstvím.

OBJECTIVE: The aim of our study is to follow patients diagnosed with breast cancer associated with pregnancy. DESIGN: Prospective follow-up study. SETTING: Department of Obstetrics and Gynecology of the 2nd Medical Faculty of the Charles University and Faculty Hospital Motol, Prague. METHODS: Between the year 2002 and 2006 12 women were reffered to our department, seven with the diagnosis of breast cancer during pregnancy, three within one year after the delivery, two pregnant after the therapy for breast cancer. A managment was sellected individually with respect to the age of pregnancy, the stage of the disease and to the decision of the women. The average age of the diagnosis, managment, way of delivery, fetal and maternal outcome were recorded. RESULTS: The average age was 31.7 years. Two patients underwent a termination of the pregnancy, other delivered a healthy newborn. Two of our patients are dead, three have a metastatic disease, one was lost for follow-up, the rest are further followed. CONCLUSIONS: Breast cancer diagnosed during pregnancy is a special and rare situation, which needs to be managed individually as there is a lack of information about such patients. These patients should be concentrated in specialized centers.

[Guideline for gynecological malignant tumors--primary complex therapy in operable stages of malignant tumors of uterus cervix]. / Guideline gynekologických zhoubných nádoru 2004--primární komplexní lécba operabilních stadií zhoubných nádoru delozního hrdla.

OBJECTIVE: Elaboration of guideline for primary treatment of operable cervical cancer. DESIGN: Review, consensus between proposers and opponents. SETTING: Department of Obstetrics and Gynecology, Charles University, Prague, 2nd Medical Faculty and Faculty Hospital Motol. METHOD: A retrospective review of published data, analysis of Czech statistics and consensus between proposers and opponents. RESULTS: Team work is essential in the diagnostic and therapeutic procedure. For the preoperative diagnostic management it is possible to perform magnetic resonance volumometry. For the treatment of early stage cervical cancer it is possible to perform sentinel lymph node mapping (SLNM) by patent blau and 99mTc together with frozen section. SLNM does not substitute systematic pelvic lymphadenectomy. For the treatment of IB2 stage cervical cancer, an alternative for primary surgery or chemoradiotherapy is neoadjuvant chemotherapy, followed by radical surgery. In other topics only minor changes were made from the 1998 guideline. CONCLUSION: The guideline for cervical cancer treatment should represent directions for clinicians and others, who participate in the process of the treatment of cervical cancer. The guidelines include all parts of the process (from diagnosis to follow up). It originated from the consensus between proposers and opponents: we voted about all parts of guideline.

[Guideline for gynecological malignant tumors 2004--primary complex therapy in operable stages of malignant tumors of vulva]. / Guideline gynekologických zhoubných nádoru 2004--Primární komplexní lécba operabilnich stadií zhoubných nádoru vulvy.

OBJECTIVE: Elaboration of guideline for primary treatment of operable vulvar cancer. DESIGN: Review, consensus between proposers and opponents. SETTING: Department of Obstetrics and Gynecology, 2nd Medical Faculty Charles University and Faculty Hospital Motol, Prague. METHOD: A retrospective review of published data, analysis of Czech statistics and consensus between proposers and opponents. RESULTS: Guideline for the diagnosis remain the same as in the proposal from 1998. We elaborated practically new guideline for surgical treatment. Wide excision or simplex vulvectomy is adequate only for stage la without angioinvasion, free margins have to be 5 mm. Standard surgical procedure is radical vulvectomy with inquinofemoral lymphadenectomy in stage 1a with angioinvasion, 1b and 2. In laterally localised lesions it is possible to perform hemivulvectomy or radical excision with inquinofemoral lymphadenectomy. Free margins have to be more than 8 mm. An alternative procedure in internally high-risk patients is sentinel node detection with radical vulvectomy (hemivulvectomy). Sentinel node detection has to by performed by combined method of blue dye and radiocoloid Tc 99 simultaneously. Bilateral inquinofemoral lymphadenectomy is indicated in case of positive sentinel node. Primary radiotherapy is indicated in higher stages, in stage 3 we can perform an exenteration with the agreement of patient. CONCLUSION: Guideline for the treatment of vulva cancer should be directions for clinicians and others, who participate in the process of treatment of the vulva cancer. Guidelines include all parts of the process (from diagnosis to follow up). All topics of the guidelines were arise from a voting of the proposers and opponents.

[Treatment of early stages of ovarian carcinoma. Evaluation of experience at the Institute of Radiation Oncology over a 10-year period (1983-1993)]. / Lécba casných stadií karcinomu ovaria. Zhodnocení zkuseností Ustavu radiacní onkologie za období deseti let (1983-93).

The authors evaluated in a retrospective study the therapeutic results of ovarian carcinoma stage FIGO I (68 patients) and FIGO II (28 patients) attained in the Institute of Radiation Oncology, Prague during the ten-year period from 1983-1993. Total survival and survival without relapse within five years are 77% in stage I and 74% in stage II. The corresponding values of five-year survival without relapse were 56% and 58% resp. Despite the fact that the therapeutic results are comparable with data in the literature, a great shortcoming is the inadequate documentation of the initial laparotomy and the very general histopathological finding, moreover without grading, in a great proportion of the patients. The authors emphasize that these shortcomings make a reliable indication of adjuvant therapy impossible, in particular in early stages of ovarian carcinoma. Despite repeated references to this shortcoming these mistakes have persisted for several decades.

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.