Undergraduate palliative care teaching in Swiss medical faculties: a nationwide survey and improved learning objectives.

BACKGROUND: In 2007, a first survey on undergraduate palliative care teaching in Switzerland has revealed major heterogeneity of palliative care content, allocation of hours and distribution throughout the 6 year curriculum in Swiss medical faculties. This second survey in 2012/13 has been initiated as part of the current Swiss national strategy in palliative care (2010 - 2015) to serve as a longitudinal monitoring instrument and as a basis for redefinition of palliative care learning objectives and curriculum planning in our country. METHODS: As in 2007, a questionnaire was sent to the deans of all five medical faculties in Switzerland in 2012. It consisted of eight sections: basic background information, current content and hours in dedicated palliative care blocks, current palliative care content in other courses, topics related to palliative care presented in other courses, recent attempts at improving palliative care content, palliative care content in examinations, challenges, and overall summary. Content analysis was performed and the results matched with recommendations from the EAPC for undergraduate training in palliative medicine as well as with recommendations from overseas countries. RESULTS: There is a considerable increase in palliative care content, academic teaching staff and hours in all medical faculties compared to 2007. No Swiss medical faculty reaches the range of 40 h dedicated specifically to palliative care as recommended by the EAPC. Topics, teaching methods, distribution throughout different years and compulsory attendance still differ widely. Based on these results, the official Swiss Catalogue of Learning Objectives (SCLO) was complemented with 12 new learning objectives for palliative and end of life care (2013), and a national basic script for palliative care was published (2015). CONCLUSION: Performing periodic surveys of palliative care teaching at national medical faculties has proven to be a useful tool to adapt the national teaching framework and to improve the recognition of palliative medicine as an integral part of medical training.

Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome of head and neck cancer treated with IMRT.

The UICC classification (TNM) represents the validated standard tool to describe tumor extent and includes prognostic information on the probability of disease control. The American Joint Committee on Cancer (AJCC) stage grouping is based on the evaluation of treatment and outcome. Gross tumor volume (GTV) might be more relevant than pure description (TNM) or stage grouping as prognostic factor for local control in head and neck cancer (HNC). Based on the observation of GTV-correlated outcome in our initial HNC patient cohort treated with IMRT, we tested the hypothesis that the GTV is the most reliable predictive tool in HNC outcome. A GTV based volumetric staging system (VS) was introduced, using two volumetric cut-off values (15 and 70 cm3). VS, TNM, and AJCC stages were assessed and correlated with outcome following primary radiation in 172 HNC patients. Analyses were based on Kaplan-Meier survival curves. VS proved to be superior to the TNM/AJCC in predicting outcome. In addition, VS enabled to stratify high- and low-risk patients in advanced TN stages. GTV represented the most important prognostic indicator in HNC treated with IMRT and is recommended to be considered for therapeutic decisions and estimation of outcome.

IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients.

BACKGROUND: Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. RESULTS: Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5-6 x 2 Gy/week to 60-70 Gy, 5 x 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 x 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients. Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. CONCLUSION: SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Localized prostate cancer in elderly patients. Outcome after radiation therapy compared to matched younger patients.

PURPOSE: To detect a difference in outcome (disease-specific survival, local tumor progression, late toxicity, quality of life) after curative radiotherapy for localized prostate cancer in elderly as compared to younger patients. PATIENTS AND METHODS: In a retrospective analysis 59 elderly patients (> 74 years old) were matched 1:2 with younger patients from the data base according to tumor stage, grading, pre-treatment PSA values and year of radiotherapy. Surviving patients were contacted to fill in a validated questionnaire for quality of life measurement (EORTC QLQ-C30). Median follow-up for elderly and younger patients was 5.2 and 4.5 years, respectively. RESULTS: Overall survival at 5 years was 66% for the elderly and 80% for younger patients. Intercurrent deaths were observed more frequently in the elderly population. There was no age-specific difference in disease-specific survival (78% vs 82%), late toxicity or quality of life. Clinically meaningful local tumor progression was observed in 15% and 14%, respectively, corresponding to data from the literature following hormonal ablation. CONCLUSIONS: There is no obvious difference in outcome including disease-specific survival, late toxicity and quality of life in elderly patients, compared to a matched younger population. A clinically meaningful local tumor progression following radiotherapy or hormonal ablation only is rare. Local radiotherapy or, alternatively, hormonal ablation is recommended to preserve local progression-free survival in elderly patients except for very early stage of disease (i.e. T1 G1-2 M0).

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: the importance of the target volume.

PURPOSE: To assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT). PATIENTS AND METHODS: Patients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C). RESULTS: Patients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module. CONCLUSION: The high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Curative radiotherapy in elderly patients with endometrial cancer. Patterns of relapse, toxicity and quality of life.

PURPOSE: To assess survival, disease-specific survival, acute and late toxicity and quality of life in patients with curable endometrial carcinoma treated with adjuvant or primary radiotherapy at the age > or = 75 years. PATIENTS AND METHODS: In a prospective study, outcome was regularly assessed in 49 patients treated between 1991 and 1995 at a median age of 78.4 years. Radiotherapy was applied using the same concept as in younger patients. Thirty-eight patients received postoperative adjuvant radiotherapy (vaginal insertions only: n = 18; external and vaginal insertions: n = 17; external radiotherapy only: n = 3), 8 patients were treated for a vaginal recurrence. Three patients received primary radiotherapy. Median pelvic dose was 39.6 Gy (ICRU) with 1.8 Gy per fraction (4 fields). Vaginal HDR radiotherapy consisted of 5 times 5 Gy at 0.5 cm depth in cases with no external radiotherapy, and of 3 times 5 Gy in addition to pelvic radiotherapy, respectively. Median follow-up was 3.2 years. The EORTC QLQ-C30 was used for self-assessment of quality of life. RESULTS: Survival and disease-specific survival at 5 years was 64% and 84%, respectively. There was no pelvic or vaginal recurrence in patients with Stage IA to IIB. Patients with positive adnexa and those treated for vaginal recurrence relapsed in 50%. Two patients (4%) did not complete radiotherapy because of severe diarrhea. Grade 4 late complications were observed in 1/38 patients following adjuvant radiotherapy and in 2/8 patients treated for a recurrence. The actuarial rate of Grade 3 to 4 complications was 7% at 3 years. Quality of life was good in most cases and remained constant over time. CONCLUSIONS: Elderly patients with endometrial cancer may be treated following the same guidelines as younger patients. Radiotherapy for a vaginal recurrence is less effective and more toxic.

[Therapy of CNS metastases]. / Therapie von ZNS-Metastasen.

Brain metastases occur in 20-30% of patients with systemic cancer and represent one of the most unfavourable prognostic parameters. In the majority of cases brain metastases are multiple and are usually treated with whole brain irradiation. The treatment of single brain metastases often includes surgery, followed by whole brain radiotherapy. Although the goal of treatment of both single and brain metastases is almost always palliation and not cure, it is important that several modes of treatment are carefully compared. In comparing different treatment regimens it should be emphasised that not only duration of survival time and time until tumour recurrence are used as outcome parameters but also the quality of life. The only way in which the results of different therapies can be compared is by means of randomised trials. As long as high quality studies are not available, any definitive assessment of the relative effectiveness of radiosurgery to standard treatment for brain cannot be defined. Radiosurgery can be used to treat patients, whose metastases recur after traditional therapies. As with other definitive therapies for patients with brain metastases, highly functional patients with well-controlled systemic cancers derive the greatest benefit from treatment with radiosurgery.

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome.

PURPOSE: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. METHODS: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H&N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). RESULTS: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of > or = grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. CONCLUSIONS: Hyperfractionated RT with concomitant CDDP is well tolerated and highly efficient in controlling moderately advanced to advanced cancers of the head and neck. Second primary tumors are the main cause of death after 3 years and were observed outside of the irradiated area, most frequently in the lung. Even after RT of large volumes to a high dose, salvage surgery can be successfully performed in individual cases. Self-reported quality of life of surviving patients is good, despite xerostomy-associated nutritional difficulties.

Radiotherapy for metastatic carcinomas of the kidney or melanomas: an analysis using palliative end points.

PURPOSE: To assess the rate and duration of response to palliative radiotherapy (RT) in patients with metastatic melanoma or renal cell carcinoma. PATIENTS AND METHODS: From 1992 to 1995, 90 patients were entered into a nonrandomized study. Goals of palliative RT were prospectively defined and subjective response was documented at the end of RT, after 2-6 weeks, and every 3 months thereafter. Most patients were treated with 5 x 4 Gy or 10 x 3 Gy. RESULTS: Relief of pain from bone lesions was observed in 26 of 40 cases, with a duration of response of 2.4 months, corresponding to 57% of the remaining lifetime. A total of 55% of patients with persistent neurologic dysfunction despite corticosteroids improved, for a duration of 2.5 months (86% of the further lifespan). Freedom from symptoms in patients treated for impending neurological complications from metastases to the brain, spine, or nerve plexus was documented for 86-100% of their lifetime. CONCLUSIONS: Despite the methodological flaws discussed, the efficacy of a short course of palliative RT for so-called radioresistant tumors is demonstrated.

[Radiotherapy of epipharyngeal carcinoma: successes and limits as examples of new treatment strategies]. / Strahlentherapie des Epipharynxkarzinoms: Erfolge und Grenzen als Beispiel neuer Behandlungsstrategien.

In treating cancer patients, disease free survival and survival have been improved during the last decade by technical progress and new systemic therapies. In radiation therapy as well as in any other cancer treatment potential long-term side effects and complications need special attention. The success of doubling tumour control by radiation therapy in patients with head and neck tumours illustrates the needs of long-term follow-ups. Cost-effectiveness has to be considered, when treatment results of RT equal surgical results, as it is often the case in head and neck tumours as well as in other malignant diseases.

Acute toxicity of curative radiotherapy in elderly patients.

AIM: One reason for obvious differences in cancer treatment of elderly patients, compared to younger patients, may be the fear of reduced tolerance at a higher age. The purpose of the study was to document acute tolerance of radiotherapy with curative intent in patients > 74 years old. Special emphasis was given to 72 patients treated to large volumes and/or high doses for gynecological carcinomas, prostate cancer of subsites of the head and neck requiring bilateral treatment of the neck including major parts of the pharynx and larynx. PATIENTS AND METHOD: From January 1991 to May 1995, 210 consecutive patients entered a prospective study to assess acute toxicity of radiotherapy given with curative intent. Median age was 79.3 (74.4 to 93.7) years. Fifty-three percent received postoperative radiotherapy, 47% radiotherapy alone. Radiation technique, fractionation and doses were the same as applied in younger patients. Tolerance was scored using a 5-point scale; in addition, pre- and post-treatment Karnofsky performance status and body weight were assessed. RESULTS: Acute toxicity leads to a dose reduction in 3 patients. The death of 1 patient with Hodgkin's disease was attributable to large field radiotherapy, and 1 case of grade 4 cystitis was noted in a patient with prostate cancer. Radiotherapy for breast cancer with or without lymph nodes imposed no problem. With appropriate supportive measures, even hyperfractionated or accelerated radiotherapy regimens for carcinomas of the head and neck were feasible in elderly patients. Radiotherapy to the pelvic region lead to severe diarrhea requiring medication in 20% of the patients. For all areas treated, higher age within the range of > 74 to < 94 years did not increase the severity of the acute radiation reactions. CONCLUSIONS: Using the same treatment schedules and techniques of radiotherapy as for younger patients, curative radiotherapy is well tolerated in patients aged > 74 years treated even when major parts of the pharynx and larynx or large volumes of the pelvis are included. Small bowel reaction (diarrhea) and pharyngeal mucositis deserve special attention and supportive care in elderly patients prone to a rapidly symptomatic dehydration.

Radiotherapy for carcinomas of the head and neck in elderly patients.

BACKGROUND/AIM: One fourth of patients with carcinomas of the head and neck present at the age of > or = 75 years, but tolerance and outcome of radiotherapy in this population is unknown from the literature. Our aim was to assess the overall survival rate in comparison to the survival probability of the normal population, and to document the efficacy of local treatment. PATIENTS AND METHODS: From 1980 to 1993, 75 patients aged 75 years or more (median 78.5 years) were treated with curative intent for carcinomas of the head and neck excluding the nasopharynx, paranasal sinuses, salivary glands and lips. Seventeen received postoperative radiotherapy, 58 were treated with radiotherapy alone. Early stage disease (T1 or T2 N0) was present in 26 patients, 27 patients presented with stage T3 and T4 any N. Eight patients received hyperfractionated radiotherapy to 74.4 Gy with 1.2 Gy twice daily. All others were treated with 1.8 to 2 Gy to a median total dose of 70 Gy in 6 to 8 weeks. RESULTS: All but 6 patients completed radiotherapy. Local control at 3 years was 83% for early stage disease, and 39% for T3 and T4 tumors. Actuarial overall survival was 30% at 5 years, compared to 63% for age-matched male and 69% for female Swiss residents, respectively. The survival curve of the patients followed the curve of the normal population after a rapid drop in survival within the first 2 years. Median time to local relapse was 3 and 4 months, respectively, for early and advanced stages, and 6 months for glottic carcinomas. Except 1 case of bone necrosis, there was no severe late toxicity observed. CONCLUSION: Although retrospective, the results suggest that the ultimate outcome in elderly patients with carcinomas of the head and neck is comparable to the course of the disease in younger patients.

[Low-dose radiotherapy of localized prostate neoplasms: How low is high enough?]. / Kleinvolumige Bestrahlung lokalisierter Prostata-karzinome: Wie klein ist gross genug?

BACKGROUND: According to the American Patterns of Care Studies, at least 70 Gy are required to achieve local control of large or undifferentiated carcinomas of the prostate. More recent data on repeated measurements of the prostate-specific antigen (PSA) cast doubt on the radiocurability of tumors with markedly elevated PSA. PATIENTS AND METHODS: With a retrospective analysis, the treatment results of local radiotherapy to mid-sized pelvic volumes with a median dose of 66 Gy (1979 to 1988, n = 118) are compared to the outcome after radiotherapy to small prostatic volumes with a median dose of 70.2 Gy (1989 to 1992, n = 126). RESULTS: Overall survival at 5 years was 65.9% and 82.3%, respectively. Patients treated at a later time had the same life expectancy as expected for the normal population. Distant disease-free survival was identical in both groups (70.4 and 74.3% at five years). Local control could not be assessed by digital rectal examination in a large part of the patients. However, in 50 patients without any pretreatment, the course of PSA was followed. Pretreatment values of > 30 ng/ml were highly predictive for "biochemical relapse" (rising values) within 2 years. Despite individual shielding of the rectum, the rate of symptomatic proctitis rose from 1.7% to 5.6% in patients treated 1989 to 1992. CONCLUSIONS: We found no negative impact of decreasing the target volume on the overall and distant disease-free survival. The rate of symptomatic proctitis has increased with higher target doses despite better shielding of the rectum, but has remained within an acceptable range. Considering the high rate of biochemical relapse and therefore the poor prognosis associated with initial PSA values > 30 ng/ml, the application of a potentially toxic dose of > 70 Gy in these patients seems hardly justified.

[Radiotherapy in prostatic carcinoma]. / Radiotherapie beim Prostatakarzinom.

Treatment of patients with prostate cancer has become one of the most frequent indications in radiation oncology. Reasons for this fact may be the increasing number of elderly patients, early diagnosis and urologists who are familiar with the possibility of tumor control by radiation. The treatment results and side effects of modern techniques are presented. Many questions concerning treatment policy remain unanswered. Due to the long natural history of prostate cancer we will have to endorse clinical trials and wait many years for their results.

Contrast-enhanced endorectal coil MRI in local staging of prostate carcinoma.

OBJECTIVE: Our goal was to evaluate contrast-enhanced MRI using an endorectal coil in detecting and staging prostate carcinoma. MATERIALS AND METHODS: Sixty patients with clinically suspected prostate carcinoma were examined by T1-weighted contrast-enhanced endorectal coil MRI at 1.5 T. Results were compared with T2-weighted images in all cases and with histologic findings following radical prostatectomy in 28 patients. RESULTS: Prostate carcinomas showed no consistent pattern of contrast enhancement. In 27 patients, the tumor enhanced less than the surrounding prostatic tissue; in 10 patients, enhancement was heterogeneous; and in 23 cases, the lesion was hyperintense compared with normal glandular tissue. With respect to tumor delineation, contrast-enhanced sequences were superior to T2-weighted images in 1 case only; in 24 patients, the tumor could not be delineated at all. However, contrast-enhanced sequences provided a higher diagnostic confidence in delineating the seminal vesicles, prostate capsule, and neurovascular bundle in nine, six, and three cases, respectively. In the operated patients, accuracy, sensitivity, and specificity for staging advanced disease were comparable for both sequences. CONCLUSION: The T2-weighted sequences remain mandatory for delineation of prostate carcinoma. Contrast-enhanced T1-weighted sequences do not improve overall staging accuracy and therefore are not warranted routinely, but should be considered in cases requiring clearer delineation of the prostate capsule and/or seminal vesicles.

Prognostic factors and outcome of incompletely resected invasive thymoma following radiation therapy.

BACKGROUND: Stage III and stage IV thymomas with significant macroscopic infiltration to the neighboring structures are rarely completely resectable. It therefore remains unclear to what extent tumors must be surgically debulked to improve prognosis. PATIENTS AND METHODS: We reviewed the cases of 31 patients with incompletely resected invasive thymoma and residual macroscopic disease who were referred to postoperative irradiation. Survival and local tumor control were analyzed. All patients were treated between 1958 and 1990 with megavoltage irradiation at doses ranging from 42 to 66 Gy. The shortest follow-up time for living patients was more than 5 years. RESULTS: The overall median 5-year survival rate was 45%. Eighteen stage III patients had a 5-year survival rate of 61% and a 10-year survival rate of 57%. Thirteen patients had stage IV disease and 5- and 10-year survival rates of 23% and 8%, respectively. Univariate and multivariate analyses confirmed a worse prognosis for stage IV disease. Epithelial or spindle-cell thymoma was associated with stage IV disease. Twenty-two percent of patients with stage III disease had epithelial or spindle-cell thymoma, versus 69% of patients with stage IV disease (P = .02 for univariate and P = .05 for multivariate analysis). Initial tumor diameter greater than 10 cm correlated with poor prognosis in the univariate analysis (P = .05). However, more importantly, debulking of tumor did not significantly improve outcome when compared with patients who received biopsy only. The median survival rate of patients with stage IVa disease did not differ from that of those with stage IVb disease. Mediastinal control was achieved in 23 patients (74%). Stage IV disease did not correlate with an increase in local treatment failure after irradiation, although epithelial or spindle-cell thymoma predisposed for local treatment failure (46% v 11%; P = .04 in univariate and P = .055 in multivariate analysis). CONCLUSION: Tumor debulking leaving macroscopic residual thymoma, as opposed to biopsy alone, does not improve prognosis when followed by radiation. Radiation therapy for local tumor control is most effective in nonepithelial-predominant thymomas.

Incidence of second solid cancer in patients after treatment of Hodgkin's disease.

PURPOSE: An analysis of the incidence of second malignant solid tumors in our patients after radiotherapy or radiotherapy plus chemotherapy for Hodgkin's disease has been performed. PATIENTS AND METHODS: 340 patients had curative treatment with mantle or paraaortic and pelvic radiotherapy (1964 to 1972) or mantle plus paraaortic and spleen or splenic pedicle or total nodal radiotherapy with or without chemotherapy (1973 to 1992) and have a follow-up of at least 1.5 years. Since 1987, after chemotherapy only modified involved fields were irradiated. All second tumors have been histologically verified. The cumulative incidence of second solid cancer of the patients have been compared with the age and sex specific expected rates according to the "Zürcher Krebsregister 1980 to 1990". RESULTS: We observed seven patients with leukemia after radiotherapy plus chemotherapy, five patients with non-Hodgkin-lymphoma and 21 patients with solid cancers after radiotherapy or radiotherapy and chemotherapy with a cumulative risk of all second malignancies of 7.0% (ten years), 30.7% (20 years) and 40.5% (24 years). Cumulative risk of second solid cancer was 3.1% (ten years), 9.3% (15 years), 23.5% (20 years) and 34.3% (24 years). Cumulative risk of second solid cancer was significantly higher than expected with no decrease of the relative risk after more than 20 years of follow-up. Comparable to the observations from Stanford, we observed a significantly higher risk of breast cancer in women less than 30 years of age at treatment. Relative risk of second solid cancer was higher after radiotherapy plus chemotherapy compared to radiotherapy alone, but the difference was not statistically significant. Nearly all patients with radiotherapy plus chemotherapy and a follow-up of ten years or more had radiotherapy with large fields. CONCLUSIONS: In patients after treatment of Hodgkin's disease with radiotherapy or radiotherapy plus chemotherapy, incidence of second solid cancer is significantly higher than expected. Incidence of second solid cancer after chemotherapy and large field radiotherapy is higher than after radiotherapy alone, but this difference is statistically not significant.

Cardiac lesions after mediastinal irradiation for Hodgkin's disease.

We analysed the risk of myocardial infarctions in 339 patients with Hodgkin's disease treated with radiotherapy (rt) with or without chemotherapy. A total of 112 patients underwent cardiac testing with echocardiography, rest and exercise electrocardiogram and myocardial scintigraphy. Nearly all patients have been treated with < 2.0 Gy per fraction to the anterior cardiac region. A significantly increased risk of myocardial infarctions or of sudden death has been observed (10 patients). No cardia events have been observed in 215 non-smokers without hypertension and without coronary artery disease (CAD) already present before rt. In the heart study group (112 patients), there were 6 patients with probable or proven CAD. Five of these 6 patients had known risk factors for CAD. Echocardiography showed sclerosis of the aortic and or the mitral valves in 34 patients. Of these patients, 2 had a slight and 1 a moderate aortic stenosis, 5 had a slight and 1 a moderate mitral regurgitation. Evidence for a disturbance of the diastolic function has not been observed. No patient had a clinically relevant pericardial lesion. In patients without risk factors for CAD, there is only a low risk of ischaemic cardiac events after modern mediastinal rt for Hodgkin's disease. Patients should eliminate the known risk factors. There is a high incidence of sclerosis of the mitral and or the aortic valves developing into clinically important lesions in few patients. Decision on the treatment strategy and the rt technique should also involve consideration of the cardiac risk. For routine follow-up, we recommend inclusion of an echocardiography in intervals between 3 and 4 years.