The rising incidence of parotid metastases: our experience from four decades of parotid gland surgery.

Secondary neoplasia in the parotid gland is increasingly frequent. We examined outcomes from 40 years of parotid surgery to analyse patterns for metastasis, review the staging procedure and discuss management. We retrospectively examined 772 consecutive cases of parotid surgery in a university hospital between 1975 and 2015 and assessed changes in incidence and management over four decades. In all, 71% percent of patients were male and 29% were female, with a mean age of 68 years, aged between 23 and 93 years. We diagnosed 683 parotid tumours of which 15.8% (n = 108) were malignant; 44% (n = 48) of all malignant lesions were metastases. The incidence of malignant tumours rose from 8% in the first decade, 14% in the second, 17% in the third to 21% in the fourth. The incidence increased even further from 10% in the first to 57% in the final decade. Most frequent tumours were metastases of squamous cell carcinoma (79%), and the majority of these lesions (87%) arose from above the clavicle, with 30 primary tumours in the skin. In most cases, the skin tumour had been excised between 6 and 24 months prior to parotid metastasis. Management consisted of surgery with neck dissection. 48 patients (67%) received adjuvant therapy, but despite aggressive multimodal treatment, disease progressed in the majority of cases, in 57% squamous cell carcinoma of the skin primaries, 67% of mucosal primaries above the clavicle and 83% of infraclavicular primaries. Parotid malignant tumours are increasing in incidence, mostly due to a rise in metastatic malignant tumours within the parotid gland, most of which are metastases of skin tumours, commonly squamous cell carcinoma. Despite multimodal therapy, their recurrence and progression rate remains high. We propose inclusion in head and neck follow-up in all cases of head and neck skin cancers.

[Significance of Secondary Mucosal Primaries in Patients with a Cervical CUP-Syndrome]. / Bedeutung des sekundär auftretenden Primärtumors bei einem zervikalen CUP-Syndrom.

BACKGROUND: We discuss the significance of an occult primary in the prognosis of cervical carcinoma with unknown primary (CUP) after completion of diagnostic and treatment. PATIENTS/METHODS: A series of 36 patients diagnosed between 2001 and 2009 underwent staging including panendoscopy, mapping and tonsillectomy, ultrasound and CT/MRI of the neck, thorax and abdomen. The patients recieved neck surgery followed by adjuvant radio-(chemo-)therapy of cervical fields as well as limited mucosal irradiation (IMRT, GHD 50 Gy). The results of tumor control and therapy-related toxicity were ascertained. RESULTS: A secondary primary of the cervical metastases was not detected during follow-up. 6 patients died from distant metastases and 1 from chemotherapy; 4 patients died from a different secondary tumour, 2 patients died intercurrently. We did not observe late toxicity but 8% of patients had Grade 3 dysphagia. DISCUSSION: Efficacy of diagnostic procedure and therapy are important in treating occult primary tumours in CUP. Our results show that omitting PET-CT, which was not available in diagnostic workup of the study-patients, did not impact negatively on the manifestation rate of mucosal primaries and/or was compensated for by intensive therapy. Distant metastases and infraclavicular secondary primaries had a negative impact for the survival. Elective therapy of a presumed occult primary tumour in CUP should be included into the therapeutic discussion considering its efficacy and toxicity.

Does high-dose radiotherapy benefit palliative lung cancer patients?: An intradepartmental comparison of two dose regimens.

BACKGROUND AND PURPOSE: The present analysis compares two palliative treatment concepts for lung cancer in terms of overall survival. PATIENTS AND METHODS: Survival data from 207 patients were used in a retrospective analysis. All patients received palliative treatment comprising either 25 Gy applied in 5 fractions or 50 Gy in 20 fractions. A subgroup analysis was performed to compare patients with a good-fair vs. poor overall condition. RESULTS: Median survival times were 21 weeks (range 6-26 weeks) for patients treated with 25 Gy in 5 fractions and 23 weeks (range 14.5-31.5 weeks) for patients treated with 50 Gy in 20 fractions (95 % confidence interval, CI; p = 0.334). For patients with a good-fair overall condition, median survival times were 30 weeks (21.8-39.2 weeks) for 25 Gy in 5 fractions and 28 weeks (14.2-41.8 weeks) for 50 Gy in 20 fractions (CI 95 %, p = 0.694). In patients with a poor overall condition, these values were 18 weeks (14.5-21.5 weeks) and 21 weeks (13.0-29.0 weeks), respectively (CI 95 %, p = 0.248). CONCLUSION: The palliative treatment concept of 25 Gy applied in 5 fractions is sufficient for radiation of lung cancer, given that there was no obvious survival improvement in patients treated with the higher total dose regimen.

Virtual simulation in patients with breast cancer.

BACKGROUND: Investigation of the feasibility and effectiveness of virtual simulation in patients receiving radiotherapy of the breast. METHODS: Twenty-three patients were included in the study. All of them underwent a course of postoperative tangential breast irradiation. The patients were prospectively randomised into two groups. Group A patients (n=11) received a conventional computed tomography -based treatment planning, group B patients (n=12) a virtual simulation. The results of both treatment planning procedures were compared. RESULTS: The treatment planning was feasible in all patients. The time expenditure could be reduced from a median of 45.0 to 16.5 min and from 55.0 to 32.0 min for the technician and physician, respectively, using virtual simulation. Furthermore the treatment planning for the patient could be reduced from a median of 45.0 min in two sessions to 16.5 min in one session. The image quality of the digital reconstructed radiographs was satisfying compared to the simulation films. The incidence and extension of set-up corrections for the patients at the first treatment were comparable in both groups. The time interval between the planning CT and the first treatment could be reduced by 31% using virtual simulation due to the omission of the conventional simulation. CONCLUSION: The virtual simulation is a feasible tool for the treatment planning of patients undergoing tangential irradiation of the breast. Compared with the conventional simulation procedure virtual simulation is superior regarding to the precision of patients marking, the quality of the reference images and, the time expenditure for the patients and medical staff.

[Value of radiotherapy in urology]. / Stellenwert der Strahlentherapie in der Urologie.

Radiotherapy of patients with prostate cancer offers an alternative to radical prostatectomy in early stages (T1-T2). In locally advanced prostate cancer a high dose or combined radiotherapy is more effective than radical surgery with concurrent lower morbidity and mortality. Recent developments in linear accelerator technique, the progress in dose calculation and planning techniques provide the means to apply higher doses to a given tumor volume while effectively protecting the surrounding normal tissue at the same time. These improvements may possibly reduce the rate of therapy related side effects or complications significantly. The combination of external beam radiotherapy and interstitial brachytherapy as well as the combination of hormone therapy and external beam radiotherapy are most likely more effective than percutaneous irradiation alone. In special cases with a very low risk of recurrent tumor an interstitial permanent brachytherapy alone is indicated. Future developments (i.e. intensity modulated radiotherapy-IMRT, combined thermo-radiotherapy, proton- or neutrontherapy) may further increase the rate of curative treatments in patients with prostate cancer.

Immediate toxicity during fractionated total body irradiation as conditioning for bone marrow transplantation.

BACKGROUND: Total body irradiation followed by bone marrow transplantation is well established as a part of the conditioning regimen in high dose therapy. The immediate tolerance of fractionated total body irradiation (FTBI) was investigated prospectively. METHODS: From January 1995 to December 1998 162 patients received a FTBI, 6x2 Gy on 3 consecutive days, lung dose 10 Gy, for allogeneic (n=112) or autologous (n=50) bone marrow transplantation. High dose chemotherapy (mostly Cyclophosphamide) was administered after the FTBI. A standardized supportive therapy was administered. The immediate toxicity of FTBI was evaluated prospectively prior to each radiation fraction using a defined questionnaire. RESULTS: Main symptoms distressing the patient during irradiation period were gastrointestinal symptoms like nausea and emesis. The prevalence of nausea per fraction increased to 26.1% after the 4th fraction, with a significant higher prevalence in children younger than 10 years at 1st and 2nd fractions. 42.6 and 22. 8%, respectively, of all patients complained of nausea and episodes of emesis, during FTBI. Mild xerostomia and parotiditis were observed in 29.9 and 7.1% of all patients. Further gastrointestinal side effects during FTBI were loss of appetite in 16.0%, indisposition in 25.3%, mild oesophagitis in 3.7% and diarrhoea in 3. 7% of the patients. During FTBI 41.4% of the patients developed a temporary skin irritation (mild erythema). Pruritus was registered in 3.7% of the patients. Headache was observed in 14.8% and Fatigue syndrome in 49.2% of women and 28.3% of men (P<0.005). CONCLUSION: FTBI is a well tolerated therapeutic regimen in high dose therapy. The 162 patients investigated revealed no severe immediate side effects.

Impact of the filling status of the bladder and rectum on their integral dose distribution and the movement of the uterus in the treatment planning of gynaecological cancer.

PURPOSE: Determination of the impact of the filling status of the organs at risk (bladder and rectum) on the uterus mobility and on their integral dose distribution in radiotherapy of gynaecological cancer. METHODS: In 29 women suffering from cervical or endometrial cancer two CT scans were carried out for treatment planning, one with an empty bladder and rectum, the second one with bladder and rectum filled. The volumes of the organs at risk were calculated and in 14 patients, receiving a definitive radiotherapy, the position of the uterus within the pelvis was shown using multiplanar reconstructions. After generation of a 3D treatment plan the dose volume histograms were compared for empty and filled organs at risk. RESULTS: The mobility for the corpus uteri with/without bladder and rectum filling was in median 7 mm (95%-confidence interval: 3-15 mm) in cranial/caudal direction and 4 mm (0-9 mm) in posterior/anterior direction. Likewise, cervical mobility was observed to be 4 mm (-1-6 mm) mm in cranial/caudal direction. A full bladder led to a mean reduction in organ dose in median from 94-87% calculated for 50% of the bladder volume (P < 0.05, Wilcoxon's matched-pairs signed-ranks test). For 66% of the bladder volume the dose could be reduced in median from 78 to 61% (P < 0.005) and for the whole bladder from 42 to 39% (P < 0.005), respectively. No significant contribution of the filling status of the rectum to its integral dose burden was noticed. CONCLUSIONS: Due to the mobility of the uterus increased margins between CTV and PTV superiorly, inferiorly, anteriorly and posteriorly of 15, 6 and 9 mm each, respectively, should be used. A full bladder is the prerequisite for an integral dose reduction.

[Palliative radiotherapy of bone metastases. A retrospective analysis of 176 patients]. / Palliative Strahlentherapie von Knochenmetastasen. Eine retrospective Analyse von 176 Patienten.

BACKGROUND: The effect of the palliative irradiation of bone metastases was explored in this retrospective analysis. The spectrum of primary tumor sites, the localization of the bone metastases and the fractionation schedules were analyzed with regard to palliation discriminating total, partial and complete pain response. PATIENTS AND METHODS: One hundred seventy-six patients are included in this retrospective quantitative study from April 1992 to November 1993. Two hundred fifty-eight localizations of painful bone metastases were irradiated. The percentage of bone metastases of the total irradiated localizations in our department of radiotherapy in the Charité-Hospital, the primary tumor sites, the localizations and the different fractionation schedules were explored. The total, partial and complete pain response was analyzed in the most often used fractionation schedules and by primary tumor sites. RESULTS: Eight per cent of all irradiated localizations in the observation period were bone metastases. There were irradiated bone metastases of 21 different tumor sites. Most of the primary tumor sites were breast cancer (49%), lung cancer (6%) and kidney cancer (6%). The most frequent site of metastases was the vertebral column (52%). The most often used fractionation schedules were: 4 x 5 Gy (32%), 10 x 3 Gy (18%), 6 x 5 Gy (9%), 7 x 3 Gy (7%), 10 x 2 Gy (5%) and 2 x 8 Gy. The total response rates in this fractionation schedules were 72%, 79%, 74%, 76%, 75% and 72%, the complete response rates were 35%, 32%, 30%, 35%, 33% and 33%. There were no significant differences between the most often irradiated primary tumor sites, the most frequent localizations and the palliation with regard to total, partial and complete pain response. CONCLUSION: There are no differences between the different fractionation schedules with regard to the pain effect of bone metastases. A palliation is ensured in 75% of all cases with a partial response of 42% and complete response of 33%. With regard to pain response these results do not justify a recommendation for a standard fractionation schedule. Current fractionation schedules such as 10 x 3 Gy for 2 weeks or 5 x 4 Gy for 1 week should be used. Another point is the recalcification in the palliative treatment of bone metastases in patients with better prognosis. The recalcification is the basis for stabilization and prevention of fractures. This aspect should be explored in prospective studies.

[Comparison of different 3-dimensional irradiation techniques in local radiotherapy of prostatic carcinoma]. / Vergleich unterschiedlicher dreidimensionaler Bestrahlungstechniken bei der lokalen Strahlentherapie des Prostatakarzinoms.

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.

Radiotherapy-induced emesis. An overview.

BACKGROUND: A significant number of patients receiving radiotherapy experience the distressing side effects of emesis and nausea. These symptoms are some of the most distressing problems for the patients influencing their quality of life. METHODS: International study results concerning radiotherapy-induced emesis are demonstrated. A German multicenter questionnaire examining the strategies to prevent or to treat radiotherapy-induced nausea and emesis is presented. An international analysis concerning incidence of emesis and nausea in fractionated radiotherapy patients is discussed. Finally the consensus of the consensus conference on antiemetic therapy from the Perugia International Cancer Conference V is introduced. RESULTS: Untreated emesis can lead to complications like electrolyte disorders, dehydration, metabolic disturbances and nutrition problems with weight loss. Prophylactic antiemetics are often given to patients receiving single high-dose radiotherapy to the abdomen. A survey has revealed that antiemetic prophylaxis is not routinely offered to the patients receiving fractionated radiotherapy. However, there is a need for an effective treatment of emesis for use in this group of patients, too. In 20% of patients nausea and emesis can cause a treatment interruption because of an inadequate control of symptoms. Like in chemotherapy strategies there exists high, moderate, and low emetogenic treatment regimens in radiotherapy as well. The most emetogenic potential has the total body irradiation followed by radiotherapy to the abdomen. Radiotherapy induced emesis can be treated effectively with conventional antiemetics up to 50%. CONCLUSION: Studies with total body irradiation, fractionated treatment and high-dose single exposures have clearly demonstrated the value of 5-HT3-receptor antagonist antiemetics. There is a response between 60 and 97%. There is no difference in the efficacy of the different 5-HT3-antagonists. High-risk patients should be prophylactic treated with 5-HT3-antagonists. The additional administration of glucocorticoids and benzodiazepins can optimize the response.

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.

Comparison of conventional and virtual simulation for radiation treatment planning of malignant lymphoma.

PURPOSE: The exact coverage of the lymph nodes and optimal shielding of the organs at risk are necessary for patients with Hodgkin's disease or malignant lymphoma to guarantee a high cure rate and a low rate of late effects for normal tissue. The purpose of this study was to compare conventional simulation and blocking with virtual simulation in terms of coverage of the target volume and shielding of the organs at risk in this highly curative patient group. PATIENTS AND METHODS: In 10 patients diagnosed with Hodgkin's disease and 5 patients with a Non-Hodgkin lymphoma radiation treatment planning for a mantle field or para-aortic field with inclusion of the spleen was performed in a conventional manner and with virtual simulation. With conventional technique, irradiation portals were defined during fluoroscopy and shielding of the organs at risk was drawn onto the simulation films, based on the information from previous X-ray films, CT or MRI scans. For virtual simulation, contouring of the target volumes and organs at risk (e.g. the kidneys) and the definition of the irradiation portals were performed with the AcQSim software package on a VoxelQ workstation (Picker Inc.) This was done in a beam's eye view environment on a currently driven CT scan in the treatment position. Both irradiation portals were compared in terms of coverage of the target volume and shielding of the organs at risk. RESULTS: Planning of a mantle field in the conventional way resulted in an incomplete coverage of the right hilus in 4/15 cases and of the left in 1/15 cases, respectively. The spleen and the spleen hilus were not covered completely in 5/15 and 6/15 cases, respectively. The left kidney was adequately shielded in only two thirds (10/15) of the conventionally planned fields. The planning time required for virtual simulation was reduced for the patient, but was increased for the physician because of the more time consuming contouring procedure compared to conventional simulation. CONCLUSIONS: Virtual simulation based on CT scans for radiation treatment planning of malignant lymphoma gives more information about soft tissue structures than conventional treatment planning. Therefore, it allows a more precise coverage of the target volumes and better shielding of the organs at risk. However, the time required for the whole procedure is increased. This is justified because of the often highly curative intention when treating this group of patients.

[Virtual simulation. First clinical results in patients with prostate cancer]. / Virtuelle Simulation. Erst klinische Ergebnisse bei Patienten mit Prostatakarzinom.

AIM: Investigation of options of virtual simulation in patients with localized prostate cancer. PATIENTS AND METHODS: Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient's skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. RESULTS: Mean differences of the patient's mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. CONCLUSIONS: The precise patient's mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarily of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.