Neoadjuvant hormonal therapy in prostate cancer - impact of PSA level before radiotherapy.

PURPOSE: To retrospectively investigate the impact of prostate specific antigen (PSA) level after neoadjuvant androgen- deprivation therapy (ADT) on biochemical relapse-free survival in patients with prostate cancer who received radical radiotherapy (RT). METHODS: Between March 2003 and March 2008, 128 men with localized prostate cancer underwent neoadjuvant ADT for 4-6 months followed by radical RT. Biochemical relapse-free survival was compared between patients with pre-RT PSA ≤ 0.1 vs > 0.1 ng/mL. RESULTS: At a median follow up of 47.3 months, biochemical relapse-free survival was significantly higher in patients with a pre-RT PSA ≤ 0.1 ng/mL compared with pre-RT PSA > 0.1 ng/mL (85.6 vs 63.2%, p = 0.0025). CONCLUSION: The current analysis demonstrating better treatment outcome in patients with excellent biochemical response to neoadjuvant ADT, supports an individualized treatment strategy.

[Five-year results of IMRT for prostate cancer - toxicity]. / Petileté výsledky IMRT karcinomu prostaty - toxicita.

BACKGROUND: Intensity modulated radiotherapy (IMRT) plays a crucial role in the treatment of prostate cancer thanks to its capacity for healthy tissue sparing. This work reports on the acute and late toxicity rates among 233 patients treated with high-dose IMRT. MATERIAL AND METHODS: From June 2003 to December 2007, 233 men with clinically localized prostate cancer underwent radical radiotherapy. One hundred sixty patients were treated with IMRT to the prostate and the base of seminal vesicles to 78 Gy in 39 fractions, 73 patients underwent simultaneous integrated boost. Prescribed doses were 82 Gy and 73,8 Gy in 41 fractions to the prostate and seminal vesicles, respectively. Late toxicity was evaluated prospectively using a RTOG/FC-LENT score. RESULTS: Thirty patients (12.8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. No acute Grade 3 or 4 GI toxicity developed. Forty two patients (18.1%) experienced acute Grade 2 genitourinary toxicity and 23 patients (9.9%) had Grade 3 GU toxicity. Grade 4 Genitourinary toxicity was observed in nine (3.8%) patients, due to a need of short-term urinary catheterization. With a median follow-up of 49.2 months, the estimated 5-year cumulative incidence of Grade 2 gastrointestinal toxicity was 22.4%. The estimated 5-year cumulative incidence of Grade 2 genitourinary toxicity was 17.7%. CONCLUSION: Intensity modulated radiotherapy enables dose escalation to 78-82 Gy with an acceptable toxicity.

[Five-year results of IMRT for prostate cancer - tumor control]. / Petileté výsledky IMRT karcinomu prostaty - kontrola nádoru.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is the method of choice in external-beam radiotherapy tolocalized prostate cancer. This work analyses five year results of IMRT with a dose of 78/82 Gy. PATIENTS AND METHODS: From June 2003 to December 2007, the IMRT technique was employed to treat 233 patients with T1-3 N0 M0 prostate cancer. It was supplemented by hormone therapy especially in high-risk patients. Two IMRT techniques were applied - IMRT with a dose of 78 Gy in 39 fractions to prostate and seminal vesicles (SV) (IMRT 78) and IMRT with simultaneous integrated 82 Gy boost to prostate concurrently with 73,8 Gy in 41 fractions to SV (IMRT SIB 82). The IMRT 78 technique was used in 160 patients (69%). Seventy-three (31%) patients with intermediate (IR) or high-risk (HR) prostate cancer without SV involvement were treated with IMRT SIB 82 technique. The PSA relapse was defined as an increase in PSA of at least 2.0 ng/mL above the nadir or in comparison to the value at the initiation of hormone therapy. Clinical relapse was defined as an occurence of distant metastases and/or local recurrence. RESULTS: The median follow-up of our patients´ population was 4.3 years (range 0.6-8.9 years). The estimated 5-year PSA relapse-free survival in low-risk (LR), IR and HR patients was 86%, 89% and 83%, respectively (p = NS). In a multivariate analysis, Gleason score (GS) 8-10 was associated with significantly higher risk of PSA relapse (RR 2.76), while higher age at the time of diagnosis significantly decreased the PSA relapse risk (RR 0.94). The estimated 5-year clinical relapse-free survival in LR, IR and HR patients was 100%, 99% and 95%, respectively (p = NS). In a univariate analysis, both GS and PSA had a significant impact on the 5-year clinical relapse-free survival - GS 2-7 97 % vs GS 8-10 88 % (p = 0.03), PSA 20 98 % vs PSA > 20 85 % (p < 0.01). CONCLUSION: Treatment of localized prostate cancer using IMRT with a dose 78/82 Gy yielded an excellent 5-year tumour control with a risk of clinical relapse being less than 5%.

Time course of late rectal toxicity after radiation therapy for prostate cancer.

Rectum and bladder are the crucial organs at risk for curative radiation therapy of localized prostate cancer. We analyzed the incidence, profile and time course of late rectal radiation toxicity. A total of 320 patients with T1-3 prostate cancer were treated with three-dimensional conformal radiation therapy (3D-CRT). The prescription dose was 70 Gy for T1 and T2 patients (n=230) and 74 Gy for patients with locally advanced T3 tumors (n=90). Late rectal toxicity was graded according to the Fox Chase modification of the Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force (LENT) criteria. The median follow-up time was 6.2 years (range 0.2-10.7 years). At 5 years, the risk for the development of grade 2 and 3 rectal toxicities was 15.6 and 7.0%, respectively. All new cases of grade 2 and 3 rectal toxicities were observed within 5 years after treatment. Prevalence of grade 2 and 3 rectal symptoms showed fluctuation with maximum at 1.5 years and the minor peak at 4.5 years. Toxicity profile changed significantly over time. The proportion of rectal bleeding within grade 2 and 3 toxicity decreased from 85% at 1.5 years to 46% at 4.5 years. Conversely, the proportion of fecal incontinence among grade 2 and 3 rectal symptoms gradually increased (0% at 1.5 years vs 27% at 4.5 years). Late rectal radiation toxicity represents a dynamic process. Rectal bleeding decreases and fecal incontinence increases over time.

[Extended field radiotherapy and high-dose brachytherapy combined with chemotherapy in patients with locally advanced cervical carcinoma]. / Radioterapie velkými poli a brachyterapie s vysokým m dávkovým príkonem s konkomitantní chemoterapií u pacientek s lokálne pokrocilým cervikálním karcinomem.

OBJECTIVE: Evaluation of results of extended field radiotherapy and high-dose rate brachytherapy combined with chemotherapy in patients with locally advanced cervical carcinoma. TYPE OF THE STUDY: A retrospective study. SETTING: Department of Oncology and Radiotherapy, University Hospital Hradec Králové. METHODS: Forty five patients with stage IIB - IVA cervical cancer and radiologically suspicious pelvic and/or paraaortic lymph nodes were treated at the Dept. of Oncology and Radiotherapy Hradec Králové with pelvic and paraaortic radiotherapy, high-dose rate brachytherapy and concomitant chemotherapy with cisplatin or cisplatin and paclitaxel. RESULTS: The 3-years disease free survival estimate was 64%. Hematological toxicity was the most limiting factor of concomitant chemotherapy. Late toxicity grade III and IV was observed in 7 patients. One patient underwent surgery due to ileus caused by lymphoma. CONCLUSIONS: Concomitant chemoradiotherapy with paraaortic fields results in high tumor control but also significant acute and late toxicity. New techniques of radiotherapy, such as intensity modulated radiotherapy, may improve the therapeutic ratio.

[Chemotherapy intensity importance in concurrent chemoradiotherapy of locally advanced cervical cancer]. / Význam intenzity chemoterapie v konkomitantní chemoradioterapii lokálne pokrocilého karcinomu hrdla delozního.

OBJECTIVE: Concurrent chemoradiotherapy with weekly cisplatin became a standard procedure in patients with locally advanced cervical carcinoma. The objective of this retrospective study was to evaluate the therapy toleration and the survival of patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy with weekly cisplatin of 40mg/m2. SUBJECT AND METHOD: From January 2000 to December 2004, 40 patients with locally advanced cervical cancer were treated with concurrent chemoradiotherapy with weekly cisplatin of 40mg/m2. Radical radiotherapy consisted of external beam radiotherapy 25 x 2 Gy to the pelvis, high-dose rate brachytherapy 6 x 4 Gy to the tumor, boost 7 x 2 Gy to the pelvic walls. 21 patients also recieved 22 x 2 Gy to the para-aortic lymphatic nodes. RESULTS: Only 16 patients recieved full five doses of cisplatin. Causes of discontinuance of the chemotherapy: acute hematological toxicity with leukopenia (10), thrombocytopenia (1), anaemia (1), increased levels of creatinine (2), profuse vomiting (1), haematemesis (1). Stage dependent two-year overall survival (OS) was 72% (IIB) against 64% (III, IVA). Two-year disease-free survival (DFS) dependent on the number of cisplatin doses was 77% (> or = 3 doses) against 56% (<3 doses) in patients with IIB stage. CONCLUSION: Acute hematological toxicity with leukopenia was the most frequent cause of discontinuance of the chemotherapy. The results of two-year OS and DFS show difference in dependence on the number of applied doses of chemotherapy. However, the difference was not significant due to a low number of patients subject to the study.

Clinical results of intensity-modulated radiation therapy (IMRT) for tumors of the head and neck region.

Intensity-modulated radiation therapy (IMRT) is an advanced form of the three-dimensional conformal radiation therapy (3D-CRT). Highly conformal dose distribution is the basic feature of IMRT. The head and neck region is suitable for this new technology since the primary tumor is often surrounded by several critical structures. IMRT offers the ability of dose escalation due to steep dose gradient towards healthy tissues. In this review, clinical results of IMRT in several head and neck sites are presented, including intracranial tumors. Parotid-sparing strategies and patterns of local-regional failures are analyzed. The possibilities of irradiation of recurrent malignancies are mentioned. In perspective, the potential of IMRT should be explored in conjunction with altered fractionation regimens, including simultaneous integrated boost (SIB). Particularly, studies with dose escalation are desirable.

Conformal radiotherapy for prostate cancer--longer duration of acute genitourinary toxicity in patients with prior history of invasive urological procedure.

The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.

The role of chemotherapy in prostate cancer. Minireview.

Hormonal therapy in disseminated prostate cancer is effective in 70-80% of patients and prolongs their lives of a mean 1-2 years. Sooner or later, androgen independence develops due to a multifactorial mechanism. A smaller part of patients may respond to second-line hormonal manipulations (antiandrogen withdrawal, adrenal enzymes synthesis inhibitors, corticosteroids). In hormone-refractory disease only about 30% of patients would respond to chemotherapy. In the standard chemotherapy the mostly used cytotoxic agents are anthracyclines, platinum derivatives, vinca alkaloids and cyclophosphamide. However, combined chemotherapy is not more effective than monotherapy. Conventional chemotherapy may improve especially the quality of life. The median survival in chemotherapy patients (6-12 months) is not significantly longer when compared with the best supportive care. In recent years the main concern has been focused on new cytotoxic drugs and different combinations with hormonal agents. In Phase II studies the combinations of estramustine with oral etoposide, estramustine with taxanes and alternating weekly regimens (doxorubicin, ketoconazole/estramustine, vinblastine) show higher response rates (53-69% of patients with prostate-specific antigen decline of more than 50%) and longer survival (13-19 months) than conventional chemotherapy.