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.

Total body irradiation is a crucial risk factor for developing secondary carcinomas after allogeneic hematopoietic stem cell transplantation in childhood.

Allogeneic hematopoietic stem cell transplantation (HSCT) has become a standard part of therapy for a variety of malignant and non-malignant disorders. With improved outcomes after HSCT, increasing attention has been drawn to late complications in long-term survivors. The development of secondary malignancies is recognized as one of the most serious complications. We have evaluated data from 426 patients (272 males, 154 females) who underwent allogeneic transplantation at a median age of 7.9 years from 1989 till 2017 and were alive more than one year after transplantation for the occurrence of secondary solid tumors. We have documented the occurrence of secondary solid tumors in 20 patients (4.7%). The median duration of the development of secondary solid cancer from HSCT was 11.7 (range, 5.4-21.5 years). 18 out of 20 patients (90%) had total body irradiation (TBI) 12-14.4 Gy as a part of a conditioning regimen. All but two had transplantation for malignant disease. All patients underwent surgery and/or chemo-radiotherapy. Eighteen are alive, and two died due to the progression of their secondary malignancy. The most frequent solid cancer was thyroid carcinoma (n=9). Cumulative incidence of secondary solid cancer in all groups was 15.2±3.9%, in a group using TBI based regimen 34.7±8.9%, in non-TBI (only chemo) group was 1.5±1.1%. Overall, the cumulative incidence is statistically significantly different between the TBI based and non-TBI (chemo only) group. The incidence and number of complications following allogeneic HSCT in childhood are increasing in time. The early diagnosis of secondary malignancies is one of the key tasks of long-life multidisciplinary post-transplant care.

Three-dimensional conformal radiotherapy versus intensity modulated radiotherapy with simultaneous integrated boost in the treatment of locally advanced head and neck carcinoma.

The treatment of locally advanced head and neck cancer (LAHNC) requires a multimodality approach. Radiotherapy with combination of chemotherapy are demonstrated to be effective, however, the treatment intensification leads to increased toxicity at the same time. The implementation of three-dimensional conformal radiotherapy (3D-CRT) allowed to irradiate the treatment volume more precisely with better surrounding healthy tissue sparing. Intensity modulated radiotherapy (IMRT) facilitated higher conformity in dose shaping to target volume. IMRT with simultaneous integrated boost (IMRT-SIB) offered the possibility to deliver individualized dose levels within one fraction and enabled escalation of the dose per fraction and radiotherapy acceleration. The aim of our study was to compare the technique of 3D-CRT and IMRT-SIB in the treatment of LAHNC and evaluate the treatment outcome and the treatment-related toxicity. 262 patients in 3D-CRT group and 263 patients in IMRT-SIB group underwent the radical treatment for LAHNC between 1/1998 and 12/2016. No statistically significant differences in locoregional control (LCR) and overall survival (OS) were found between the two groups. Acute toxicity and xerostomia were significantly reduced in the patients treated by IMRT-SIB. IMRT-SIB is a safe radiotherapy method where less toxicity was proven without compromising local control and overall survival.

[Nephroblastoma -  30-years period of its treatment in the University Hospital Motol, Prague]. / Nefroblastom -  30 let lécby ve Fakultní nemocnici v Motole.

INTRODUCTION: Nephroblastoma (Wilms tumor - WT) is the most common solid tumor of kidney in children. We present treatment development of WT at the Department of Pediatric Hematology and Oncology, Charles University in Prague, 2nd Faculty of Medicine and University Hospital Motol (KDHO) in the Czech Republic over 30 years. Patients that were treated prior to access to the International Society of Pediatric Oncology (SIOP) protocols are considered to be the historical group, then we have patients treated according to SIOP 9, SIOP 93-01 and SIOP 2001 protocols as full participants of SIOP studies. PATIENTS AND METHODS: Between January 1980 and April 2009, we treated 330 patients with WT at KDHO: 91 patients in historical group (1980-1988), 94 pts in SIOP 9 (1988-1993), 80 pts in SIOP 93-01 (1994-2001) and 65 pts in SIOP 2001 (2002-2009). Overall survival (OS) and event-free survival (EFS) were analyzed by Kaplan-Meier test. RESULTS: The overall ten-year EFS was 81.2% and OS 87.6%. Fifty-eight patients from the 330 (17.6%) had metastases at diagnosis, EFS without metastatic process was 84.6% compared to 65.4% with metastasis presented at diagnosis (p = 0.0003), OS was 70.7% compared to 91.2% (p < 0.0001). One hundred and seventy patients (51.5%) were treated with preoperative chemotherapy and/or radiotherapy, whereas 158 patients (47.5%) underwent primary nephrectomy; EFS and OS did not differ: neoadjuvant vs primary nephrectomy EFS was 81.2% vs 80.9% (p = 0.85), OS 89.4% vs 85.4% (p = 0.38). Sixty (18%) patients experienced disease recurrence; OS after relapse was 33%. In the historical group, EFS and OS were 85.7% and 91.2%. In patients treated according to the SIOP 9 protocol, EFS and OS were 68.1% and 74.5%, resp. In patients treated according to SIOP 93-01, it was 83.6% and 93.7%, resp. and in patients treated according to 87 SIOP 2001, it was 7% and 95.4% (p = 0.001 and p = 0.0008), resp. CONCLUSION: WT is a well treatable disease. The aim for the future is to maintain the current very good survival while minimizing the treatment intensity.

Influence of neoadjuvant treatment of rectal carcinoma on operability and incidence of distant metastases.

In the Czech Republic, rectal carcinoma does not only represent a medical problem, but also a socio-economic one. At our department, we treated totally 266 patients with rectal carcinoma in the years 1998 through 2006. Among our patients, neoadjuvant treatment led to a reduction in size of the tumour in 37.6 %, in 50.8 % the size did not change. In T3 tumours, the reduction in size was observed in 36.7 % of the patients and did not change in 56 %; in T4 tumours, the reduction in size was observed in 60% of the patients. In 88 % of the patients who underwent the operation, no residual tumour was found, in 9 % of patients, a residual tumour was detected. In 19 % of the patients, a local recurrence of the tumour was detected. A statistically significant relationship was proved between the appearance of the metastatic disease and the presence of angioinvasion and the size of the primary tumour according to the Duke's classification (Tab. 1, Fig. 4, Ref. 20).

[The role of radiotherapy in the treatment of malignant lymphomas - recommendations of the Czech Lymphoma Study Group]. / Postavení radioterapie v lécbe maligních lymfomu - doporucení Kooperativní lymfomové skupiny.

BACKGROUND: Indication of radiotherapy in lymphoma treatment is an important strategic decision requiring comprehensive expertise. It also calls for a better definition of the position of radiotherapy in clinical practice. DESIGN: This position paper represents a consensus between hematooncologists and radiation oncologists on the role of RT in treatment of different histological types and stages of malignant lymphomas. The discussion was underway within professional societies of both specializations (Czech Lymphoma Study Group for the hematooncologists and the Society of Radiation Oncology, Biology and Physics for the radiation oncologists). RESULTS: The consensus presented here was reached in early 2012 and draws on evidence-based medicine and clinical practice. Besides defining the role of radiotherapy in lymphoma treatment, this paper also gives specific recommendations on total doses of radiotherapy in lymphoma treatment. CONCLUSION: These recommendations will supplement 7th edition of "Diagnostic and treatment guidelines in patients with malignant lymphoma" scheduled for publication in 2013.

[Treatment results in patients treated from 1980 to 2004 for Wilms' tumour in a single centre]. / Lécebné výsledky pacientu lécených v letech 1980-2004 na jediném pracovisti pro nefroblastom.

BACKGROUNDS: The principle behind the treatment of nephroblastoma has been similar for at least 4 decades, based on vincristine and dactinomycine, radiotherapy in selected stages. The last three decades have been characterised by the aim to reduce the intensity and length of treatment. DESIGN: To retrospectively compare survival rates and treatment success in a cohort of patients aged under 19 years, treated from 1980 to 2004 at a single centre by five consecutive treatment protocols. MATERIALS AND METHODS: The outcome was evaluated in patients treated consecutively by two protocols established at the centre before 1980 and modified in 1986, and from 1988 consecutively by three accepted protocols, SIOP9, SIOP93 and SIOP2001. RESULTS: Overall survival as well as event-free survival rates were evaluated by Kaplan-Meier functions in 315 patients (52.7% women). The average age at diagnosis was 3.9 +/- 2.9 years, median 3.3, range 0.01-17.2 years. Age over 12 years in 2.2% patients. The average follow-up time was 13.1 +/- 7.8, median 13.6, range 0.2-27.8 years. The original 104 weeks of protocol KDO86 treatment had a 10-year overall survival rate of 91.9 +/- 3.2%. Overall survival significantly fell with radiotherapy reduction in lower clinical stages and treatment diversification in protocols with substantial treatment length reduction. Overall survival returned to the original value of KDO86 only in 1994, when SIOP93 was accepted with a 10-year overall survival rate of 92.47 +/- 3.0% and event-free survival 85%, with similar trends in the latest protocol, SIOP2001. In the entire cohort two coincident malignancies (tumour duplicities) were found: one B-lymphoma, one neuroblastoma. A second malignancy occurred in one patient--superficial spreading melanoma. CONCLUSION: from the retrospective view the accepted SIOP9 protocol has a significantly worse outcome in both the overall survival and in event-free survival rate compared with the original therapy. Only the SIOP93 and SIOP2001 protocols accepted after 2003 have an acceptable 10-year overall survival rate (around 92%) as well as event-free survival (85%) with substantially reduced length and intensity of treatment, lowering the risk of late effects.

Preoperative radiotherapy for locally advanced rectal cancer and prognostic factors influencing outcome.

The aim of presented study was to evaluate the impact of different factors on survival, local recurrence and development of metastatic disease in patients with rectal cancer treated with preoperative radiotherapy or 5-fluorouracil (5-FU) based concurrent chemoradiation. Retrospective clinical evaluation was performed in 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period January 1998 - March 2003. Tumor extent was evaluated by CT and/or MRI and/or TRUS examination and tumor biopsy was performed during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. Computed tomography localisation of target volume was used for 3D radiotherapy treatment planning. Accelerated short term regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998-2000 and normofractionated regimen (40-50 Gy/20-25 fractions/4-5 weeks) was performed in 86% of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The 2-year overall survival (OS) was 84% and 5-year OS was 60% following radical resection. The important prognostic factors affecting survival were postradiotherapy determined pathological staging (p=0.005), postradiotherapy tumor grade (p<0.001) and the presence of angioinvasion and/or perineural spread (p=0.023). Prognostic factors for disease-free survival were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy tumor staged T4 (p=0.048) and in presence of angioinvasion and/or perineural spread (0.049). Age, tumor location, histological grade before radiotherapy and tumor downstaging were not statistically significant for survival and/or for local recurrence rate. The best survival rates were obtained in patients with postradiotherapy grade 1 tumors (5-years survival 100%), tumors without angioinvasion and perineural spread (5-years survival 65%) and in patients who obtained complete remission after preoperative radiotherapy (5-years survival 86%).

[Protection of reproductive functions in patients with tumors]. / Ochrana reprodukcních funkcí u nemocných s nádorovým onemocnením.

BACKGROUND: Survival from cancer continues to improve. Antimitotic therapy can induce failure of spermatogenesis and oogenesis, gonadal disturbances and infertility. Recent advances in reproductive medicine have opened opportunities for the preservation of reproductive potential of patients with cancer. The aim of our study was to analyse by a multidisciplinary team the contemporary state of art and proposal of the Czech model of fertility preservation starting in childhood and continuing through the whole reproductive period. METHODS: This paper highlights the problems associated with gonadal failure as a consequence of therapy for malignancy in childhood, adolescence and adulthood. Analysis of these problems served as a principle for the management strategy for fertility preservation. CONCLUSIONS: Patients undergoing treatment for malignancy are at the high risk of gonadal damage and infertility. Therefore, alternative treatments with less gonadal toxicity and different treatment protocols were evaluated. Fertility can be preserved with the freezing and banking of spermatozoa, embryos, and oocytes obtained prior to the cancer treatment. In female patients (starting in puberty) pharmacological preservation of gonads with gonadoliberin analogues is also possible. Chance for the future fertility preservation for children offers freezing and thawing of primordial follicles and spermatozoa obtained during the gonadal biopsies. Long-term follow-up study by a multidisciplinary medical team is necessary.

[Treatment of Hodgkin's disease using the German Study Group protocol. Personal experience and results]. / Lécba Hodgkinovy choroby podle protokolu Nemecké studijní skupiny. Nase zkusenosti a výsledky.

The article present an evaluation (02/1999) of the study of primary treatment of Hodgkin's disease (HD) according to the third generation of the German Hodgkin's Disease Study Group (GHSG), and our experience with this treatment strategy. HD7 study of early stages HD showed better results (fewer relapses) for combined chemo and radiotherapy than for radiotherapy alone (2x ABVD + extended field radiotherapy compared to extended field radiotherapy alone). HD8 study of intermediate stage HD did not show any difference between chemotherapy 2x (COPP + ABVD) combined with radiotherapy extended field, or involved field. Due to the long-term consequences (especially secondary neoplasm), in the current (fourth) generation protocol extended field radiotherapy in early and intermediate stage HD has been replaced by a combination of lesser toxic chemotherapy and involved field radiotherapy. HD9 study of advanced HD. The standard treatment at present of COPP/ABVD (A) was compared with the new chemotherapeutic regimen, BEACOPP baseline (B) and escalated (C). The first evaluation of this study (1996) showed better results in the case of BEACOPP. The latest evaluation showed significantly better results for the escalated version. This is best illustrated by the low percentage of disease progression (C 2%, B 8%, A 12%, p < 0.05). Therefore, DHSG is considered to be the new standard for treatment of advanced stage HD. OUR RESULTS: Between 1995-1998, 54 patients with primary HD were treated at the FN Královaké Vinohrady, Prague according to the third generation GHSG protocol. Of these, 5 patients (9%) according to HD7, 14 (26%) according to HD8 and 35 patients (65%) according to HD9. Our results correspond to those of the whole GHSG, but they can not be statistically evaluated because of the small number of patients involved.

[The quality of documentation in patients after conservative surgical procedures in breast carcinoma and its effect on subsequent therapy]. / Kvalita dokumentace u pacientek po konzervativních chirurgických výkonech pro karcinom mlécné zlázy a její vliv na následnou lécbu.

The quality of data was evaluated in 50 patients referred for adjuvant treatment to the Department of Radiotherapy and Oncology, University Hospital "Královské Vinohrady" after conservative surgery for breast cancer. The authors suggest improving the cooperation between surgeon and radiation oncologist. The purpose of this study is to establish the criteria for conservative surgery of breast carcinoma and to evaluate, if the data provided by surgery and pathology departments are sufficient for radiation oncologist to complete high quality postoperative radiotherapy.

The diagnostic value of x-ray methods, endoscopy, oriented gastrobiopsy and brush cytodiagnostics in malignant and benign diseases of the stomach.

Studies in 59 patients with various diseases of the stomach (37 cancerous and 22 non-cancerous ones) are reported and their results commented on. Each of the patients underwent, beside clinical examinations, laboratory tests, and radiography, fibrogastroscopy with oriented gastrobiopsy and brush cytodiagnostics respectively. At the cytologic preparation of the material, three methods have been used: direct smears, smears from sediment as obtained after brush rinsing in alcohol (50%), and paraffine embedding of sediment. Out of 37 patients with carcinoma of the stomach, positive and suspicious data resulted at the clinical examination (chiefly suspected ones) in 27, as against 25 at the X-ray one, and 35 at fibrogastroscopy. Oriented gastrobiopsy yielded positive results in 27 cases, whereas oriented brush cytodiagnostics in 35 out of 37 patients. An evaluation of the various cytologic methods in the diagnostics of cancerous and non-tumorous diseases of the stomach has been made. The complex examination of the patients yields the most accurate diagnosis, contributing to the ascertainment of benign and malignant diseases of the stomach.