Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Re-irradiation for painful heel spur syndrome. Retrospective analysis of 101 heels.

PURPOSE: Painful heel spur syndrome is a common disease with a lifetime prevalence of approximately 10 %. One of the most effective treatment options is radiotherapy. Many authors recommend a second or third series of radiation for recurrent pain and partial or no response to the initial treatment. As the results of re-irradiation have not been systematically analyzed the aim of this study was to document the results of repeated radiation treatment and to identify patients who could benefit from this treatment. MATERIAL AND METHODS: The analysis was performed on patients from 2 German radiotherapy institutions and included 101 re-irradiated heels. Pain was documented with the numeric rating scale (NRS) and carried out before and directly after each radiation therapy as well as for the follow-up period of 24 months. The median age of the patients was 56 years with 30.1 % male and 69.9 % female patients. Pain was caused by plantar fasciitis in 72.3 %, Haglund's exostosis in 15.8 % and Achilles tendinitis in 11.9 %. Repeated radiation was indicated because the initial radiotherapy resulted in no response in 35.6 % of patients, partial response in 39.6 % and recurrent pain in 24.8 %. RESULTS: A significant response to re-irradiation could be found. For the whole sample the median NRS pain score was 6 before re-irradiation, 2 after 6 weeks and 0 after 12 and 24 months. Of the patients 73.6 % were free of pain 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain. CONCLUSION: Re-irradiation of painful heel spur syndrome is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.

[Anxiety and depression in cancer patients during the course of radiotherapy treatment]. / Angst und Depressivität bei Tumorpatienten im Verlauf der radioonkologischen Behandlung.

BACKGROUND: Undergoing radiotherapy is often associated with severe impairment of quality of life in cancer patients. Especially psychosocial aspects like anxiety and depression play a major role. The aim of this study was to closely analyze anxiety and depression during the course of radiotherapy treatment. METHODS: A total of 60 patients, who received radiotherapy because of a tumor disease between June 2005 and April 2006, were included in the prospective study; 57 (95%) patients were primarily treated with radiotherapy. In 72% of the cases the intention to treat was curable, in 18% palliative. Anxiety and depression (HADS-D) were assessed at three points in time: before (A) and after (B) radiotherapy treatment (RT), and 6 weeks after finishing RT at the follow-up appointment (C). RESULTS: Before therapy (A), 41% of the treated patients showed positive or marginally positive symptoms of anxiety and 33% symptoms of depression. The symptoms of anxiety significantly decreased during the course of therapy. The proportion of patients with a positive score of anxiety dropped from 16% at the beginning of RT (A) to 9% after the RT (B; p = 0.04). In addition, there was an increase in the number of patients who scored negatively with regard to anxiety from 59% (A) to 72% (B; p = 0.04). With regard to the median score of anxiety, no statistically significant change (p > 0.05) was observed during therapy, while for depression, the number of positively tested patients also decreased significantly during the course of therapy from the beginning of RT (A, 14%) to the first follow-up appointment (C, 9%; p = 0.02). Furthermore, the number of negatively tested patients rose by 8% (p = 0.02). During the whole course of the study, the median score of depression decreased from 6 (A) to 5 points (C; p = 0.01). CONCLUSION: More than one third of the treated patients suffered from positive or marginally positive symptoms of anxiety and depression. This present study showed a decrease of anxiety and depression symptoms during the course of radiotherapy.

[FDG-PET-CT based imaging of retropharyngeal lymph nodes with its impact on radiotherapy]. / Die Darstellung retropharyngealer Lymphknoten in der FDG-PET/CT und ihre Bedeutung für die Radiotherapie.

BACKGROUND: In about 20% there is an involvement of the retropharyngeal lymph nodes in patients with locally advanced carcinoma of the hypopharynx and cervical esophagus. A case report should demonstrate the diagnostic and therapeutic impact of FDG-PET/CT in the radiotherapeutic management of a locally advanced carcinoma of the hypopharynx in special consideration of the RPLN. PATIENT AND METHOD: A pretherapeutic FDG-PET/CT was performed with the patient fixed in the radiotherapy mask in order to integrate the anatomic and metabolic information into the radiotherapy planning system by an exact matching of the data. RESULTS: Only the FDG-PET could detect a retropharyngeal lymph node involvement (RPLN) by an intensive glucose utilisation with a consecutive modification of the target volume and dose increase in this region. CONCLUSION: This case report demonstrates that FDG-PET/CT facilitates the imaging of metabolic active and otherwise hardly detectable lymph nodes in locally advanced head and neck cancer with consequences on target volume definition and dose application in radiotherapy.

The prognostic value of anaemia at different treatment times in patients with locally advanced head and neck cancer treated with surgery and postoperative radiotherapy.

AIMS: We report a retrospective mono-institutional analysis of anaemia (< 12 g/dl) at different treatment times (preoperative, postoperative, before radiotherapy and nadir levels during radiotherapy) in head and neck cancer patients treated with surgery and postoperative radiotherapy. The study objective was to determine whether, and at which time points, anaemia had a significant effect on the end points overall survival and local recurrence-free survival (LRFS). MATERIALS AND METHODS: The end points for the statistical analysis in 130 patients were LRFS and overall survival. A univariate analysis (Log-rank test) was carried out on the following variables with potential end point-related impact: gender, T, N, G, American Joint Committee on Cancer (AJCC) stage, tumour site, resection status, overall treatment time (OTT), radiotherapy treatment time (RTT) and preoperative, postoperative, pre-radiotherapy and nadir levels of haemoglobin during radiotherapy. Individual variables with a significant effect (P=0.05) were then subjected to multivariate Cox regression analysis. RESULTS: The median overall survival was 59 months. The univariate analysis showed that AJCC stage (P=0.0268), resection status (P=0.0407), preoperative haemoglobin level (P=0.0087), postoperative haemoglobin level (P=0.0035), RTT (P=0.0042) and OTT (P=0.0343) significantly influenced overall survival. OTT (P=0.0130) and postoperative haemoglobin (P=0.0243) had a significant effect on LRFS. The multivariate Cox regression analysis showed postoperative haemoglobin < 12 g/dl and OTT>100 days to be independent negative prognostic factors for both end points. CONCLUSIONS: Postoperative acute anaemia < 12 g/dl and an OTT>100 days were independent negative prognostic factors for LRFS and overall survival in patients with head and neck cancer treated with surgery and postoperative radiotherapy.

[Survival with distant metastatic disease in head and neck cancer. A retrospective analysis]. / Uberleben mit hämatogen metastasierten HNO-Tumoren: Eine retrospektive monozentrische Analyse.

QUESTIONS: The objective of this retrospective analysis was to investigate parameters with a potential impact on survival in a collective of 114 patients with distant metastatic disease after head and neck cancer. PATIENTS AND METHODS: The primary endpoint was the survival with distant metastatic disease, the secondary endpoint was overall survival. Primary therapy, local recurrence, second neoplasms, palliative chemotherapy (CHT) and radiotherapy (RT), as well as Karnofsky performance status (KPS) at the time of diagnosis of the metastases were analyzed as potential impact parameters using the log-rank test with subsequent Cox regression analysis. RESULTS: Palliative CHT (P=0.0020) and KPS (P=0.0011) had a significant positive impact on the median survival probability with metastases (8.2 months) using the log-rank test, KPS at the time of diagnosis of metastases remained as an independent prognostic parameter in the Cox regression (P=0.0013). Primary therapy, local tumor control and KPS had a significant positive influence on the median overall survival probability (18.5 months) univariately (P=0.0139, P=0.0106, P= 0.0096) and multivariately (P=0.0123, and P=0.0063, P=0.0197, respectively). CONCLUSIONS: KPS at the time of diagnosis of metastases is an independent prognostic parameter for both endpoints. Lacking evidence for life prolongation, palliative therapies should therefore first and foremost focus on the stabilization of the KPS.

[Instruction in medical ethics during clinical training for medical students: report on experience in radio-oncology]. / Unterricht in Medizinethik im Rahmen der klinischen Ausbildung von Medizinstudenten: Ein Erfahrungsbericht aus der Radioonkologie.

The article gives a review of the current state of education in medical ethics in Germany. The issue is considered from the viewpoint of radio-oncology. Both the pertinent literature and our own experience in teaching medical ethics are presented. In October 2003, medical ethics was integrated into the curriculum of medicine. The aim was to train competence in the field of personal attitudes and to intensify skills of moral reasoning. Our own experiences are positive, which is in accordance with the reports of other working groups. Most of the students were interested in education in medical ethics and looked upon ethical training as being an important part of their studies. Medical students are interested in ethical education during the clinical period of their studies, which has been taken into account since the actual change of the curriculum. Radio-oncologists as specialists in other clinical fields can offer important contributions when they discuss clinical cases from the viewpoint of medical ethics. The long-term effect of such an education will become the subject of future research.

Intracavitary afterloading boost in anal canal carcinoma. Results, function and quality of life.

BACKGROUND: First clinical data on a new intracavitary afterloading boost method for anal canal carcinoma is reported. PATIENTS AND METHODS: 20 consecutive patients (T1 5%, T2 70%, T3 20%, T4 5%; N0 75%, N1 10%, N2 15%; all M0) treated with external beam pelvic radiotherapy (median dose 56 Gy, range 46-64 Gy), simultaneous 5-FU and mitomycin (in 75%) and an intracavitary afterloading boost (one or two fractions of 5 Gy at 5 mm depth) were analyzed after a mean +/- SD follow-up for living patients of 4.4 +/- 2.1 years. Quality of Life (QoL) and anorectal manometry parameters were assessed in ten colostomy-free survivors. RESULTS: Overall, recurrence-free and colostomy-free survival at 5 years were 84%, 79% and 69%, respectively. No death was tumor-related. The only local failure was successfully salvaged by local excision. All three colostomies were performed for toxicity. Resting pressure and maximum squeeze pressure of the anal sphincter were reduced by 51% and 71%, as compared with control subjects, but quality of life was similar compared to healthy volunteers. CONCLUSION: The described regimen is highly effective but associated with increased toxicity.

Influence of treatment technique on dose-volume histogram and normal tissue complication probability for small bowel and bladder. A prospective study using a 3-D planning system and a radiobiological model in patients receiving postoperative pelvic irradiation.

PURPOSE: A prospective study was undertaken to evaluate the influence of pelvic irradiation techniques on the dose-volume histograms of organs at risk and to analyze its possible clinical relevance using radiobiological models. PATIENTS AND METHODS: For 20 patients receiving postoperative pelvic irradiation because of rectal cancer a 3-field technique (3-FT), a 4-field technique (4-FT) and an opposing field technique (OFT) were designed by a 3-D planning system (Helax, TMS). Dose-volume histograms (DVH) of small bowel, urinary bladder and planning target volume (PTV) were analyzed. The normal tissue complication probability (NTCP) was determined by the radiobiological model of Lyman and Kutcher using the tolerance data of Emami. RESULTS: Median dose to the PTV did not differ between the 3 techniques (3-FT/4-FT/OFT: 99.2%/98.6%/98.1% of the prescribed dose; p > 0.05). Although the median dose to the urinary bladder was lower for the 3-FT than for the 4-FT (44.7% vs 60.3%; p < 0.001), there was no difference in the calculated NTCP (0.0% vs 0.0%; p > 0.05). Using multiple field techniques both the dose to and the treated volume of the urinary bladder were significantly lower than using the OFT. As a consequence of this the late NTCP of the bladder was higher for the OFT (5.46%). Although the median dose to the small bowel was lower for the 3-FT than for the 4-FT (30.8% vs 54.5%; p < 0.005), the fractional part of small bowel within the high-dose region (90% isodose) was higher for the 3-FT (10.6% vs 8.2%; p > 0.05). Thus the calculated NTCP was higher for the 3-FT (0.79 vs 0.44) than for 4-FT. For the OFT the median dose to small bowel was 69.9% and the small bowel volume within the high-dose region was 57.8% resulting in a late NTCP of 9.36% (OFT vs 3-FT/4-FT: p < 0.05). CONCLUSION: Using multiple field techniques both the dose to the organs of risk and the fractional part of risk organs within the high-dose region can be reduced significantly. As a consequence of this a lower NTCP was calculated for the 3-FT and the 4-FT than for the OFT. Using the biological model a small, but significant difference between a 3-FT and a 4-FT was demonstrated in favor to the 4-FT.

The Internet as a source of medical information. Investigation in a mixed cohort of radiotherapy patients.

BACKGROUND: The widespread use of the internet has influenced patterns of medical information for tumor patients. The present study examines the use of various media and, in particular, the application of the internet, in a mixed cohort of radiotherapy patients. PATIENTS AND METHODS: All patients undergoing radiotherapy at the University of Würzburg were analyzed simultaneously in May of 2000 using a newly developed 9-item questionnaire. Questions related to the importance of various media for medical information (grading from 0 = unimportant to 2 = very important) and previous internet use. The data was correlated with clinical information from the patients' charts. RESULTS: In 95% of patients (n = 139) questionnaires were evaluable. Of 8 media, television (mean score 0.94), patient brochure (0.83) and newspaper (0.76) were considered most important for medical information while the internet ranged last (0.24). Whereas 61.2% knew the internet as a source of medical information, only 11.5% had searched the internet themselves and 15.1% had received internet information from family or friends. Only 24.1% from these 2 groups had discussed the information with their physician. The rates of internet use were substantially higher in subgroups with younger age, higher education and palliative treatment. CONCLUSION: The importance of the medium internet for the information of tumor patients is currently still low but likely to increase based on demographic factors.

Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function.

In 22 colostomy-free survivors of curative-intent radiation therapy or chemoradiation for anal carcinoma, measurement of the Gastrointestinal Quality of Life Index (GIQLI) revealed a mean 114 of a maximum 144 points, as compared to 121 in healthy volunteers (n = 150) and 113 in patients with benign anorectal diseases (n = 325). Sixteen patients underwent anorectal manometry to determine anal sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), rectal compliance (RC) and relaxation of the internal anal sphincter (RIAS). SL, RP and MSP were significantly lower in anal carcinoma patients than in healthy volunteers. Complete continence was detected in 56% of patients.

Long-term survival following postmastectomy locoregional recurrence of breast cancer.

Only a few reports describe long-term survivors following locoregional recurrence of breast cancer after mastectomy. We analyzed 145 patients who were treated for an isolated postmastectomy breast cancer recurrence at our department between 1979 and 1992. All patients were free from distant metastases at the time of recurrence. Nineteen of these patients remained free from distant metastases after a follow-up of more than 10 years following recurrence. Clinical and histopathological characteristics of these 19 patients were analyzed. Primary tumors were small with almost all being T1 or T2 primaries. The majority of survivors had negative axillary node status (16/19 [84%]). Locoregional recurrences were mainly chest wall recurrences (16/19 [84%]) and all recurrences were smaller than 5 cm (19/19). Only 7 patients showed a typical scar recurrence. Sixteen patients had a single recurrent nodule. Early recurrences (<1 year after mastectomy) were rare (n=2). Treatment of recurrence consisted of tumor excision in all cases followed by radiotherapy in 16 patients (including 6 patients who had undergone elective irradiation following mastectomy), hormonal therapy in 6 and chemotherapy in 1 case. In all patients local control at the recurrence site was achieved. Cure after postmastectomy recurrence seems possible in a subgroup of patients (small primary tumor with negative axilla, small and solitary chest wall recurrence) provided adequate therapy is prescribed. Treatment of these patients should not be regarded as palliative therapy.

Preoperative irradiation versus the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following total hip replacement: the results of a randomized trial.

PURPOSE: Previous studies showed the effectiveness of early preoperative (4 h before operation) irradiation for prevention of heterotopic ossification (HO) after total hip replacement. This procedure can result in logistic problems, if there is a great distance between the department of radiotherapy and the orthopedic clinic. To avoid these organizational problems a prospective study was undertaken to analyze the effectiveness of preoperative irradiation on the day preceding surgery (16-20 h before operation). METHODS AND MATERIALS: Between 1995 and 1996, 100 patients were randomized to receive a prophylactic therapy for prevention of heterotopic ossification. Forty-six patients were irradiated with 7 Gy single dose within 16-20 h before operation. Fifty-four patients were treated with nonsteroidal anti-inflammatory drugs (NSAID) (Voltaren resinat 2 x 75 mg/day for 2 weeks). Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analyzed and defined as the historical control group. RESULTS: Incidence of heterotopic ossification was 47.8% in the 7 Gy preoperative group (Brooker Score I: 36.9%; II: 8.7%; III: 2.2%; IV: 0%) and 11.1% in the NSAID group (Brooker Score I: 9.3%; II: 1.8%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 7 Gy group (p < 0.01). Analyzing the clinically significant heterotopic ossification (Brooker Score III and IV) there was no significant difference between the two treatment arms (p > 0.05). In the untreated historical control group the incidence of heterotopic ossification was 65% (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%). Referring to overall and to clinically relevant heterotopic ossification the incidence of HO was greater in the control group than in the prophylactically treated groups (p < 0.05). CONCLUSION: Irradiation within 16-20 h before operation and use of NSAID (Voltaren resinat) can reduce the incidence of clinically relevant heterotopic ossification after total hip replacement.

Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement.

PURPOSE: A randomized trial was undertaken to assess the comparative efficacy of early postoperative irradiation with either 5 or 7 Gy vs. the use of nonsteroidal antiinflammatory drug (NSAID) for prevention of heterotopic ossification (HO) following prosthetic total hip replacement (THP). METHODS AND MATERIALS: Between 1993 and 1994, 301 patients were randomized to receive postoperative irradiation (5 or 7 Gy) or NSAID. One hundred and thirteen patients were treated with NSAID (indomethacin 2 x 50 mg/day for 1 week), 93 patients were irradiated with a single 7 Gy fraction, 95 patients with a single 5 Gy fraction. The treatment volume included the soft tissues between the periacetabular region of pelvis and the intertrochanteric portion of the femur. X-rays of treated hips were obtained immediately and 6 months after surgery. Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992, were analyzed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 16.0% in NSAID-group (Brooker Score I: 8.0%; II: 6.2%; III: 1.8%; IV: 0%), 30.1% in 5 Gy group (Brooker Score I: 24.7%; II: 4.3%; III: 1.1%; IV: 0%), and 11.1% in 7 Gy group (Brooker Score I: 11.6%; II: 0%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 5 Gy group (p < .015), respectively, between the 7 Gy group and the 5 Gy group (p < .0001). No significant difference was noted in the influence of overall HO between the NSAID and the 7 Gy group (p > 0.3). Analyzing the clinically significant HO (Brooker Score III and IV) patients irradiated with 7 Gy developed less HO than those treated with NSAID (p = 0.003). Incidence of HO was greater in the untreated historical control group (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%) than in all three prophylacticly treated groups. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement with single a 7 Gy fraction is the most effective postoperative treatment schedule in prevention of clinically significant heterotopic ossification. This therapy modality is more effective than irradiation with a single 5 Gy fraction or use of NSAID.

Prevention of heterotopic ossification after total hip replacement. A prospective, randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation.

We have carried out a prospective, randomised study of prophylaxis for heterotopic ossification (HO) comparing indomethacin for 7 and 14 days, acetylsalicylic acid, and fractional (4 x 3 Gy) or single exposure of 5 or 7 Gy irradiation after operation. We initially had 723 patients (733 hip replacements), but after withdrawals there were 685 hips of which 18.4% developed HO; 14% were grade I, 2.9% grade II and 1.5% grade III of the Brooker classification. We compared the results between these groups with those of a matched control series and found that indomethacin, 2 x 50 mg for 7 and 14 days, and postoperative irradiation of 4 x 3 Gy or 1 x 7 Gy, significantly reduced the development of HO compared with the control group. Patients in the acetylsalicylic acid group and those with a single irradiation of 5 Gy after operation developed significantly more ossification than those in the indomethacin and other irradiation groups. We suggest the use of 2 x 50 mg of indomethacin with mucoprotection for seven days as prophylaxis against HO after total hip replacement for all patients. A single irradiation of 7 Gy is recommended for patients who have developed HO after previous operations or to whom administration of indomethacin is contraindicated.

Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis.

PURPOSE: The outcome of patients with local-regional breast cancer recurrence after mastectomy often is described as fatal. However, certain subgroups with favorable prognoses are thought to exist. To determine these favorable subgroups, we analyzed prognostic factors for their influence on postrecurrence survival by univariate and multivariate analysis. METHODS AND MATERIALS: Between 1979 and 1992, 145 patients with their first isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases were treated at the Department of Radiation Oncology of the University of Wurzburg. Thirty-nine percent of patients (n = 67) had had postmastectomy radiotherapy, representing 7% of patients who had received routine postmastectomy irradiation at our institution. Systemic adjuvant hormonal therapy had been applied in 24% and systemic chemotherapy in 19% of patients. Several combinations were used. Treatment of recurrences consisted of surgical tumor excision in 74%, megavoltage irradiation in 83%, additional hormonal therapy in 41%, and chemotherapy in 12% of patients, employing different combinations. Local control in the recurrent site was achieved in 86%. Median follow-up for patients alive at the time of analysis was 8.9 years after recurrence. We tested different prognostic factors, including prior treatment and treatment of recurrence, for their influence on postrecurrence survival, using univariate and multivariate analysis. RESULTS: Eighty-two of the 145 patients (57%) developed distant metastases within the follow-up period. Metastases-free rate was 42% at 2 years and 36% at 10 years following recurrence. With development of distant metastases, the survival rate deteriorated. Recurrences appeared within the first 2 years from primary surgery in 56% of patients, and in 89% within 5 years. Overall, 2-year and 5-year survival rates following local-regional recurrence were 67% and 42%, respectively. Univariate analysis revealed statistically significant worsening of survival rates for pT3 + 4 primary tumors, primary axillary lymph node involvement, tumor grading 3 + 4, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, negative estrogen (ER) and progesterone (PR) hormonal receptor status, postmastectomy chemotherapy and hormonal therapy, short time to recurrence (< 1 year), combined recurrences and supraclavicular site of recurrence, non-scar recurrence, size of the largest recurrent nodule > 5 cm, multiple recurrent nodules, no surgical excision of recurrence, small target volume of irradiation, chemotherapy for recurrence, and no local control within the recurrence site. The 2-year and 5-year survival rates ranged from 68% to 94%, and from 33% to 65%, respectively, in the favorable subgroups compared to 2-year and 5-year survival rates ranging from 20% to 59% and 0% to 35%, respectively, in the unfavorable subgroups. Multivariate analysis showed that site of recurrence and number of recurrent nodules have the strongest influence on postrecurrence survival, but time to recurrence, age at time of recurrence, local control in recurrent site as well as primary pT and axillary status, and the presence of tumor necrosis in the primary tumor specimen showed additional independent influences on survival. Thus, we identified a highly favorable subgroup of patients with a single chest wall or axillary recurrent nodule (in a patient aged > 50 years), a disease-free interval of > or = 1 year, pT1-2N0 primary tumor, and without tumor necrosis, and whose recurrence is locally controlled. This group (12 patients) had 5- and 10-year survival rates of 100% and 69%, respectively. CONCLUSION: We conclude that locoregional recurrence of breast cancer following mastectomy is not always a sign of systemic disease. Our data support previous findings, that subgroups with favorable prognosis exist and they still have a chance for cure, demanding comprehensive local treatment. (ABSTR