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Background and purpose This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts developing the national evidence-based anal cancer guideline in Germany. Materials and methods We conducted a systematic review and meta-analyses of interventions for the treatment of stage I to III anal squamous cell carcinoma (SCCA). We systematically searched several databases and included any randomised controlled trial (RCT) assessing the pre-specified patient populations, regardless of the interventions studied. Non-randomised controlled studies of selected, pre-specified interventions were included if RCTs were not available or contained insufficient information. Where possible, we conducted meta-analyses and critically assessed confidence in the effect estimates using the GRADE approach. Results Our searches yielded 10,325 (25 October 2018) and 889 hits (update search on 18 July 2019). Among the 41 studies (47 publications) included, we identified 19 comparisons of interventions for SCCA, and confidence in the effect estimates ranged from very low to high. Most RCTs compared various chemoradiation regimes. For other treatment options, such as local excision in early stages or different radiotherapies, we mostly identified comparative cohort studies. Conclusion Our findings indicate that, in most clinical situations, primary chemoradiation based on 5-FU and MMC is still the gold standard. However, treatment options for stage I anal cancer, particularly of the anal margin, as well as newer treatment approaches should be investigated in future RCTs. Overall, our findings may help health care professionals and patients make informed decisions about treatment choices.

Background The number of anal cancer diagnoses has been rising steadily, so that the incidence has doubled in the past 20 years. Almost all anal cancers are induced by persistent infection with human papillomaviruses. Hitherto the care of patients with anal cancer has been heterogeneous and little experience exists with the primary management of anal cancer. Methods The guideline was developed in accordance with the requirements of the German Guideline Program in Oncology. In line with the GRADE approach, the certainty of the evidence was assessed on the outcome level following a systematic literature search. Interdisciplinary working groups were set up to compile suggestions for recommendations, which were discussed and agreed upon in a formal consensus conference. Results Ninety-three recommendations and statements were developed. No high-quality evidence was available to support recommendations for or against the treatment of stage I anal cancer with local excision alone as an alternative to chemoradiotherapy. Chemoradiotherapy is the gold standard in the treatment of stages II–III. Among other aspects regarding the timing and extent of response evaluation after chemoradiotherapy, the guideline panel recommended against obtaining a biopsy in the event of complete clinical response. Owing to lack of confidence in the available evidence, only open recommendations were given for treatment of stage IV. Conclusion This evidence-based clinical practice guideline provides a sound basis for optimizing the interdisciplinary, cross-sector care of anal cancer patients. Among other areas, gaps in research were identified with respect to the care of patients with early-stage or metastatic anal cancer. Approaches such as chemoradiotherapy combined with regional deep hyperthermia require further investigation. The role for immunotherapy in the management of metastasized anal cancer has also been insufficiently explored to date.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer. Quality of life is an important factor when discussing therapy options for high-risk prostate cancer. This study evaluated adverse effects and health-related quality of life (HRQOL). MATERIALS AND METHODS: Ninety male patients (median age, 71 years; range, 50 to 79 years) with high-risk prostate cancer underwent HDR-BT after EBRT between December 2009 and January 2017 with a median follow-up of 43 months. A total of 57 patients (69.5%) answered the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients questionnaire (QLQ-C30; ver. 3.0), and 8 patients died during follow-up. In order to put the results of this study in context, we compared the results with reference data from the EORTC QLQ-C30 Scoring Manual. Correlations of prostate-specific antigen (PSA) values, International Prostate Symptom Score, and HRQOL measures were calculated. RESULTS: The study participants reported better physical functioning and better global health compared with the reference data, but worse social, role, and cognitive functioning. We found negative statistically significant correlations between the last-measured PSA value and social functioning (p>0.01), cognitive functioning, pain, and constipation (all p

Purpose To investigate the value of second-opinion evaluation of multiparametric prostate magnetic resonance imaging (MRI) by subspecialised uroradiologists for the detection of significant cancer in transperineal fusion prostate biopsy. Methods The evaluated data included age, PSA (ng/ml), PSA density, Gleason score, digital rectal examination (DRE), prostate volume of 149 patients. Twenty-seven patients (18%) had no previous prostate biopsy, 114 patients (77%) had a previous negative biopsy, and 8 patients (5%) were on active surveillance. Using PI-RADS v2 scores for mpMRI a second report was performed by a specialist uroradiologist. In all cases a subsequent transperineal biopsy was performed with at least 2 cores per target and additional background systemic cores. Initial and second-opinion radiology reports were evaluated for detection of any cancer and Gleason score (GS) 7-10 cancer, including positive predictive value and negative (NPV) and compared by Fisher's exact test. Results At transperineal biopsy, 51 % (76/149) of patients had a GS 6-10 prostate cancer (PCa), 27 % (40/149) of patients had a GS 3 + 3 PCa and 12 % (18/149) a GS 3 + 4 and 12 % (18/149) had a GS ≥4 + 3 PCa. Agreement between initial and second-opinion reads was observed in 57.7% (86/149; kappa value = 0.32). The detection of clinically significant cancers with second-opinion reads was significantly higher (0.61; 17/28) compared to initial reads (0.35; 17/49); P = 0.034. Conclusions Second reading of prostate mpMRIs by subspecialised uroradiologists significantly improved the positive predictive value for detection of clinically significant prostate cancer and showed a trend towards improved NPV for MRI-negative cases where biopsy could be safely avoided. Urologists should be aware that the experience of the reporter will affect the report when making decisions if and how to obtain biopsies. Reporter experience may help to reduce overcalling and avoid over-targeting of lesions.

High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D’Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

Although 15-25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB.Forty patients with anal cancer underwent 1 ml Tc(99m)-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (HE) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation.SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan--four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation.Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.

Background: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used to monitor response to multimodality cancer treatment. Preoperative short-co

We evaluated the feasibility of the sentinel lymph node technique to refine staging and potentially individualize therapy for anal cancer. Seventeen patients with cancer of the anal canal underwent peritumoral injection of 99mTc-colloid, followed 17 hours later by lymphoscintigraphy. A selective lymph node biopsy (SLNB) was attempted in 12 of 13 cases with scintigraphically detected SLNs. Lymph node metastases were present in 5 of 12 cases (42%); in 2 of these 5 cases, micrometastases were detected only by immunohistochemical staining. Hence, SLNB refines the diagnostic workup for anal cancer and provides an accurate basis for individualized therapy.

The largest subgroup of patients with metastasised urological malignancies are those with metastases of the bone. Lesions of bones frequently reduce the patients quality of life. Therefore a sufficient therapy is crucial. First of all the appropriate diagnostic procedure of the lesion/lesions is necessary because e the right choice of diagnostic measures may already improve quality of life. Besides the most frequently used local irradiation a systemic radiotherapy may be the adequate therapy in patients with disseminated disease. Renal cell-, bladder and penile cancer respectively are the urological malignancies frequently metastasising into the brain. Adequate diagnostic procedures and therapy are crucial to the patients quality of life for the remaining lifetime. Besides a whole brain irradiation as standard therapy stereotactic radiotherapy is a high precision tool to destroy intracerebral tumour. There are many other locations of metastatic disease (i.e. lymph node or soft tissue metastasis, et cetera) where palliative external beam irradiation may provide relief from symptoms such as pain, lymph oedema or bleeding and thus increase quality of life. Psychological and social care are of great value besides symptom oriented therapy (i.e. radiotherapy, drugs, et cetera) to achieve an optimal palliation/quality of life.

PURPOSE Four different three-dimensional planning techniques for localized radiotherapy of prostate cancer were compared with regard to dose homogeneity within the target volume and dose to organs at risk, dependent upon tumor stage. PATIENTS AND METHODS Six patients with stage T1, 7 patients with stage T2 and 4 patients with stage T3 were included in this study. Four different 3D treatment plans (rotation, 4-field, 5-field and 6-field technique) were calculated for each patient. Dose was calculated with the reference point at the isocenter (100%). The planning target volume was encompassed within the 95% isodose surface. All the techniques used different shaped portal for each beam. Dose volume histograms were created and compared for the planning target volume and the organs at risk (33%, 50%, 66% volume level) in all techniques. RESULTS The 4 different three-dimensional planning techniques revealed no differences concerning dose homogeneity within the planning target volume. The dose volume distribution at organs at risk show differences between the calculated techniques. In our study the best protection for bladder and rectum in stage T1 and T2 was achieved by the 6-field technique. A significant difference was achieved between 6-field and 4-field technique only in the 50% volume of the bladder (p = 0.034), between the 6-field and rotation technique (all volume levels) and between 5-field and rotation technique (all volume levels). In stage T1, T2 6-field and 4-field technique in 50% (p = 0.033) and 66% (p = 0.011) of the rectum volume. In stage T3 a significant difference was not observed between the 4 techniques. The best protection of head of the femur was achieved by the rotation technique. CONCLUSION In the localized radiotherapy of prostate cancer in stage T1 or T2 the best protection for bladder and rectum was achieved by a 3D-planned conformal 6-field technique. If the seminal vesicles have been included in the target volume and in the case of large planning target volume other techniques should be taken for a better protection for organs at risk e. g. a 3D-planned 4-field technique box technique.

Background The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control. Methods and design Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4–6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function). Discussion Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.

A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer.Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993).Before starting treatment, a PSA value ofor =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall.The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.