Favorable radiation field decrease in gastric marginal zone lymphoma : Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL).

PURPOSE: Long-term impact of stage-adapted field reduction in a large cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT). PATIENTS AND METHODS: Prospective analysis of paper records of 290 patients with stage IE-IIE gMZL, treated in 78 radiotherapeutic institutions in Germany from 1992-2013. Stage-adapted radiation fields decreased from extended field (EF) to involved field (IF) over the course of three consecutive prospective trials of the German Study Group on Gastrointestinal Lymphoma (DSGL). Treatment results were compared between the three cohorts. RESULTS: Overall collective with median age of 60 years, slight male predominance (m:f = 1.1:1) and ratio of disease stage I:stage II = 2.1:1. Median follow-up 6.4 years in total: 13.0 years in the first gastrointestinal study (GIT 1992), 8.2 years in the second (GIT 1996) and 4.7 years in the third study (DSGL 01/2003). Stage-adapted radiation field decrease together with further technological development led to reduced relative frequencies of acute/chronic adverse effects and until now was accompanied by lower disease recurrence. The third study design with smallest field size (IF in stage I, locoregional EF in stage II) achieved the best survival outcome at the 5­year follow-up (overall survival 92.7%, event-free survival 89.5% and lymphoma-specific survival 100.0%). Disease relapse observed in 10 patients. Cumulative incidence of disease-specific death was 1.7% of the followed patients. Primary disease stage associated with lymphoma-specific survival. CONCLUSION: Stage-adapted reduction towards IF in gMZL resulted in favorable adverse effects, local control and survival rates. These results support further decreases in modern RT of gMZL.

Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer-Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control. METHODS AND MATERIALS: Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/ß = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints. RESULTS: The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively). CONCLUSIONS: The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL.

The 15-year outcomes of high-dose-rate brachytherapy for radical dose escalation in patients with prostate cancer - a benchmark for high-tech external beam radiotherapy alone?

PURPOSE: Dose escalation using high-dose-rate brachytherapy (HDR-BT) is an established treatment method for prostate cancer. First, long-term results were previously published (specific Kiel method). This study aims to evaluate 10-/15-year outcomes of Kiel Protocol 1 (1986-1992). METHODS AND MATERIALS: Conformal external beam radiotherapy (EBRT) was delivered to the pelvis (50 Gy per conventional fractionation) along with an HDR boost to the prostate amounting to a combined biologic equivalent dose in 2 Gy per fraction of 117.25 Gy (α/ß = 3). The HDR-BT was performed in two fractions of 15 Gy to the peripheral zone of McNeal. The EBRT-clinical target volume covered the full pelvis. The analyzed cohort totaled 122 patients. The reported end points were overall/cancer-specific survival, local recurrence/distant metastasis rates, and biochemical (BC) control rates according to American Society for Therapeutic Radiology and Oncology/Phoenix definitions. All end points were calculated using the Kaplan-Meier method and the log-rank test in univariate analyses. RESULTS: The mean follow-up time was 116.8 months. The 5-, 10-, and 15-year survival rates were 81%, 62.1%, and 45% for overall survival; 92.1%, 83.1%, and 75.3% for cancer-specific survival; 92.5%, 91.4%, and 83.9% for local recurrence-free survival; and 83.8%, 81.2%, and 69.8% for distant metastasis-free survival, respectively. American Society for Therapeutic Radiology and Oncology-defined BC tumor control rates at 5, 10, and 15 years were 81.1%, 74%, and 67.8%, respectively. According to Phoenix, the BC control rates at 5, 10, and 15 years were 77.8%, 69%, and 63.6%, respectively. CONCLUSIONS: The long-term results for the combination of HDR-BT and EBRT continue to show excellent results, providing high equivalent dose in 2 Gy per fraction and high disease control rates. These outcomes were reproducible for the extended follow-up period ranging up to 21.9 years.

Treatment of acute radiodermatitis with an oil-in-water emulsion following radiation therapy for breast cancer: a controlled, randomized trial.

BACKGROUND: A side effect of radiotherapy for breast cancer is acute radiodermatitis. It is a common practice to keep irradiated skin dry on account of data from the 1950s that suggested this regimen limits dermatitis. However, severe dryness of the skin induced by irradiation results in itching and discomfort. Dry skin is characterized by scaliness, epidermal barrier dysfunction, and reduced stratum corneum hydration, and these signs and symptoms are reduced by treatment with an emulsion. PATIENTS AND METHODS: We performed a randomized, controlled, open-label study with 66 patients (ITT population), treating the irradiated skin in one group (n = 34) with an oil-in-water emulsion (WO1932), while leaving the other group untreated (n = 32). Clinical scoring (ONS radiation skin reaction scoring, pruritus) and biophysical measurements (stratum corneum hydration and transepidermal water loss (TEWL), as a marker of skin barrier function) were determined at day 1 (directly after termination of the radiation therapy), day 8, and day 47 (± 7). RESULTS: Irradiation increased the ONS score and pruritus, whereas skin hydration and TEWL were reduced. The primary hypothesis that the increase in skin hydration was significantly greater in the emulsion-treated compared to the untreated group as early as after 8 days of treatment could not be confirmed. At the end of the study (day 47 ± 7), however, normalization of stratum corneum hydration was more advanced in the treatment group compared to the untreated group and nearly reached the values of the contralateral healthy breast skin. ONS score and pruritus also revealed an advantage for the emulsion-treated group. TEWL did not show significant changes during emulsion treatment. No adverse events were caused by the treatment regimens CONCLUSION: Treatment of radiodermatitis with an oil-in-water emulsion was well tolerated, enhanced stratum corneum hydration, improved clinical indicators, and provided relief from itching.

Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification.

BACKGROUND: Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically addressed. METHODS: Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years. RESULTS: Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years). CONCLUSION: The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.

[Cosmetic results after breast conserving carcinoma treatment in patients with intramammarian seromas]. / Kosmetische Ergebnisse nach brusterhaltender, radiologischer Mammakarzinomtherapie bei patientinnen mit intramammären seromen.

INTRODUCTION: There were 373 patients irradiated after breast conserving carcinoma treatment. A planning computed tomography revealed in 97 of these patients seromas and tissue defects exceeding 2cm in diameter. The cosmetic results in those patients and the impact of seromas herein had to be evaluated. PATIENTS AND METHODS: Mean age was 59 years. A quadrant resection was performed in 17.5 percent of the patients, a segmental resection in 27.8 percent and a tumour excision in 54.6 percent. Radiation therapy was applied with the Linear accelerator and 6 MeV photons up to a total dose in the residual breast of 50 Gy followed by a boost dose to the former tumour bed of 10 Gy. A distinct evaluation and documentation of therapy related side effects and the resulting cosmesis was done in 51 patients. RESULTS: In all the examined seroma patients there were moderate acute skin reactions grade 1 to 3. As late effects in 82.3 percent scar indurations were noticed. At the skin 51 percent showed enhanced pigmentation, 68.6 percent atrophia and only 11 percent teleangiectasia. Subcutaneous fibrosis occurred in 56,9 percent of the patients, 78.4 percent of the women had breast asymmetries. In 41.2 percent there were a lymphedema subcutaneously, in 72.5 percent impaired sensibility. The overall cosmetic result documented with a 5 point score was "very good" (score 1) in 19.6 percent and "good" (score 2) in 33.3 percent, 37.3 percent were "satisfactory" (score 3) and 9.8 percent "bad" (score 4) respectively. No "very bad" results (score 5) were seen. CONCLUSIONS: The cosmetic results in the examined group of seroma and hematoma patients were inferior to those reported in the literature. We conclude that postoperative seroma and hematoma have an adverse effect on the resulting cosmesis and that their frequency and extent have to be reduced in future by the responsible surgeons.

20 years of experience in static intensity-modulated total-body irradiation and lung toxicity. Results in 257 consecutive patients.

PURPOSE: To analyze lung complications after allogeneic or autologous transplantation following total-body irradiation (TBI) with compensators, so-called sIMRT (static intensity-modulated radiotherapy). PATIENTS AND METHODS: Between 1983 and 1998, 257 patients with different hematologic malignancies underwent TBI in six fractions to a total dose of 12 Gy within 3 consecutive days (212 with 11 Gy lung dose) prior to allogeneic (n=174) or autologous (n=83) transplantation. 40 patients were <16 years of age. Minimum follow-up time was 5 years. Median follow-up period was 110 months (13-231 months). RESULTS: 5-year survival rate was 47.9%, 5-year tumor-related mortality 23%, 5-year treatment-related mortality 29.2% (12 Gy lung dose: 53.3%+/-14.6%, 11 Gy: 24.1%+/-5.7%). Interstitial pneumonitis (IP) developed in 28 of 257 patients (10.9% +/- 3.8%). IP incidences in the allogeneic and autologous groups were 14.4% (+/-5.6%) and 3.6% (0-7.6%), respectively. IP incidences with 12/11 Gy lung dose were 22% (+/-12%)/8.5% (+/-3.7%). IP mortality was 9.3% (+/-3.6%). 13 of 28 patients with IP had a cytomegalovirus infection, five an acute graft-versus-host disease grade IV of the lungs. IP incidences with 12/11 Gy lung dose were 25% (9-50%)/4.2% (0.2-19.1%) in patients <16 years, and 20.7% (9.4-37.4%) and 13.3% (+/-6.5%) in older patients after allogeneic transplantation. CONCLUSION: Compensator-generated static intensity-modulated TBI with a total dose of 12 Gy and a lung dose of 11 Gy is a modern and comfortable treatment with moderate lung toxicity, small dose inhomogeneities and little setup failure before transplantation. Especially patients <16 years of age benefit from lung dose reduction.

[Preoperative radiochemotherapy for advanced oral cavity tumours : the Kiel DOSAK experience regarding curability and quality of life]. / Die präoperative Radio-Chemo-Therapie beim fortgeschrittenen Mundhöhlenkarzinom : Die Kieler DOSAK-Erfahrung bezüglich Kurabilität und Lebensqualität.

BACKGROUND: According the guidelines of the German-Austrian-Swiss Council for maxillary and facial tumours (DOSAK), patients with advanced oral cavity tumours underwent preoperative radiochemotherapy followed by radical surgery. The results were to be evaluated with regard to curability and quality of life and compared with the current literature. PATIENTS AND METHODS: Between 1993 and 1998, 52 patients were treated. Radiotherapy up to a total dose of 36 Gy was combined with one cycle of cisplatin (12.5 mg/m2, days 1-5) chemotherapy. Besides clinical data concerning radiogenic toxicity and surgical complications, quality of life after therapy was of special interest. RESULTS: Three years after therapy 33 of 52 patients (63.5%) were alive, and after 5 years 19 of 33 patients (57.6%) were still alive. Seven patients (14.6%) had a local recurrence. Side effects of radiotherapy according RTOG scoring were minor; only one patient (1.9%) had grade 3 toxicity. Of 48 patients, 9 (18.7%) had no surgical complications. Quality of life was good in only 14 patients (29.2%); all the other patients (70.8%) suffered from impaired quality of life. CONCLUSIONS: Preoperative radiochemotherapy in advanced oralcavity carcinomas with subsequent radical surgery is an effective treatment regarding long-term survival. The treatment is burdened by lasting impaired quality of life. High scientific priority should hence be directed to a steady improvement of quality of life in these patients.

[Perspectives of radiation therapy in benign diseases]. / Perspektiven der Strahlentherapie gutartiger Erkrankungen.

PURPOSE: The numbers of patients with nonmalignant diseases referred for radiation therapy had to be evaluated for the last 4 years. PATIENTS AND METHODS: In the years 2002, 2004, and 2005 radiation therapy was performed in 61, 40, and 26 patients, respectively. Regularly, more women than men were treated, median age annually was 57, 54, and 55 years, respectively (Table 1). The radiotherapy scheme was not modified within the evaluated period. RESULTS: The proportion of nonmalignant diseases among all patients treated decreased from 4.7% in 2002 to 3.3% in 2004 and 2.2% in 2005, respectively. A shift was noticed toward the treatment of four main diseases (endocrine orbitopathy, prevention of heterotopic ossification, meningeoma, tendinitis, Table 2). The number of referring physicians decreased from 19 to six. CONCLUSION: Due to administrative restrictions for treatment in hospitals, budget restrictions in private practices and lasting, insufficient revenues for radiotherapy in nonmalignant diseases, radiation therapy for the entire group of benign diseases is endangered.

[A quantitative study of MRI-based treatment planning for the percutaneous radiation therapy of brain tumors]. / Eine quantitative Studie zur MRT-basierten Bestrahlungsplanung der perkutanen Therapie von Hirntumoren.

This study examined to which extent treatment plans for brain tumors can be constructed with a commercial treatment planning system (TPS) based on MRI data only. CadPlan 6.4.7 was used as TPS. In particular, differences between MRT-based and conventional CT-based plans were examined systematically. The quantification of the retrospective evaluation was carried out by the point-wise dose difference and the gamma-distribution. In this study the gamma-distribution did not appear advantageous over the dose difference for the tolerance range (point-wise dose difference < 3%, distance criterion LLL 5 mm). The calculated dose distribution showed large differences (up to 103%) at the boundary of the treatment fields, in the regions of the head contour, and in areas with air inclusions and significant bone structures. The inner parts of the fields, and therefore the actual target volume, revealed only small deviations in the range of-2% in the homogeneous distribution.

[Results of radiation therapy in periarthritis humeroscapularis]. / Ergebnisse der Strahlentherapie bei Periarthropathia humeroscapularis.

BACKGROUND: Radiation therapy is applied in painful degenerative shoulder diseases. Aim of this work was to evaluate the contribution of radiation therapy to symptomatic improvement in periarthritis humeroscapularis. METHODS: Ninety-four patients with periarthritis humeroscapularis were treated in two institutions. Mean age was 68 years, sex distribution were 32 men and 62 women. In 58 cases the right side was affected, left in 36 cases. At single doses of 0.75 Gy once a week a total dose of 6 Gy was applied (Fig. 1). The treatment effect was evaluated by the standardized von Pannewitz-score at the end of the treatment up to 6 months thereafter. RESULTS: The treatment results of all the 94 patients were documentated at the end of therapy. Seventy-one patients were followed at least for further 4 months. Radiogenic side-effects were not noticed. The symptoms of 54 patients (57.4%) were improved or vanished, in 40 cases the symptoms were not significantly affected (42.6%) (Table 1). Four months after therapy 42 of 71 patients were improved (59.2%), 29 unchanged (40.8%) (Table 2). The treatment effect occured typically up to 2 months after therapy, there were no age-related differences. Also in recurrent radiation therapies the symptoms improved, in 80 percent after one preceding therapy (Table 3), however only in 31.2 percent after multiple prior radiotherapies (Table 4). CONCLUSION: Radiation therapy is effective in the symptomatic treatment of periarthritis humeroscapularis. Treatment should be performed early after initial conservative treatment prior to any invasive therapy.

[Retrospective results of radiation therapy of the eustachian tube in chronic otitis media]. / Retrospektive Ergebnisse der perkutanen Strahlentherapie der Tuba Eustachii bei chronischer Otitis media.

BACKGROUND: The treatment results of symptomatic radiation therapy of the Eustachian tube in chronic otitis media had to be evaluated retrospectively. PATIENTS AND METHODS: Between 1980 and 1997, 66 patients were referred for therapy. The median age was 58 years. In the clinical presentation, all the patients had a hearing impairment, 35 patients complained of pain, 21 had otorrhea. In their history, 20 patients indicated chronic recurrent infections. The complaints lasted for 4.7 years in the median, primary conservative (adstringentia, antibiotics) and surgical treatment (paracentesis, tympanic tubule, tympanoplastic) did not lead to lasting cure. In 40 of 66 patients, finally radiation therapy was done of both Eustachian tubes. With opposed fields and cobalt-60 photons a total dose of 6 Gy at single doses of 1 Gy, three times a week, was applied. Under the causes for exclusion of radiation therapy were non-acceptance of the patients (nine), prior radiation therapies (six) or spontaneous improvement after initial presentation in our department. The treatment results were evaluated by interviews of the patients and regular otorhinolaryngological examinations. RESULTS: There were no side effects noticed. 28 of 40 (70%) patients reported a significant improvement that could be verified by objective otorhinolaryngological examinations. In the group of 26 nonirradiated patients, 22 could be interviewed indicating in 16 cases (72%) that the complaints were unchanged and chronic otitis media was lasting. In a subgroup analysis concerning the duration of otitis media radiation therapy proved more effective in an acute and subacute stadium of disease of up to 5 years duration, while the patients resistant to radiation therapy were entirely in a chronic stage of disease exceeding 5 years duration. CONCLUSIONS: Radiation therapy is an effective tool for symptomatic improvement of the therapy-resistant chronic otitis media. A dose of 6 Gy seems to be sufficient to achieve an antiinflammatory effect. Radiotherapy should be applied earlier after initial conservative and surgical treatment.

Interstitial brachytherapy in the head and neck region: when has imaging for treatment planning to be performed?

BACKGROUND AND PURPOSE: The relation of real and virtual anatomy in 3D treatment planning is influencing the quality of a brachytherapy treatment. Aim of this study was to evaluate how far prior to plastic tube implantation for fractionated interstitial brachytherapy performed imaging is appropriate for treatment planning purposes in regard to iatrogenic, morphologic changes of anatomy. MATERIAL AND METHODS: Until April 1, 2001, 51 patients were included in this examination. Primary tumor sites were in the base of tongue (35), oro-/hypopharynx (9), floor of the mouth (4) as well as soft palate (3). Cross section imaging (MRI) in all the patients was performed before and three to six days after implantation of plastic tubes. To evaluate the morphologic alterations due to implant procedure and postimplant edema, distances were measured between two anatomically clearly defined landmarks of whom one had to be invariant to applicator implantation. RESULTS: Between two anatomical landmarks initially mean standard distances were measured: Vertebra-pharyngeal mucosa 1.46 cm, mandibular-pharyngeal wall 3.14 cm, mandibular tip-base of tongue 5.12 cm, tongue width 4.77 cm. The comparison of pre- and postimplant MRI then revealed mean distance alterations: Vertebra-pharyngeal mucosa 3.1 mm, mandibular-pharyngeal wall 4.2 mm, mandibular tip-base of tongue 5.9 mm, tongue width 6.0 mm. CONCLUSIONS: Mean applicator induced anatomic deviations between 3.1 and 6.0 mm compared to pre-implant anatomy, can severely change the target dose distribution. Basis of 3D-treatment planning therefore has to be always postimplant cross sectional imaging with adequate soft tissue depiction.