Influence of demographic change on the demand for radiotherapy using forecasted predictions for prostate cancer in Germany.

PURPOSE: Demographic change will lead to an increase in age-associated cancers. The demand for primary treatment, especially oncologic therapies, is difficult to predict. This work is an attempt to project the demand for radiation therapy (RT) in 2030, taking into account demographic changes using prostate cancer (PC) as an example. MATERIALS AND METHODS: Using the GENESIS database of the Federal Statistical Office, we retrieved demographic population projections for 2030 and retrospective demographic surveys from 1999 to 2019. Additionally, we queried incidence rates for PC in the respective age groups of 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, and +85 years from 1999-2019 via the Federal Cancer Registry of the Robert Koch Institute. We used a regression method to determine the age-dependent correlation between the incidence of PC and the population size of the respective age group by combining the data from 1999 to 2019. This information was used to calculate the incidence rates in the age groups of the expected population for 2030 and the expected new cases of PC in 2030. Finally, we extrapolated the indications for the demand for RT based on data from the Report on Cancer Incidence in Germany from 2016. RESULTS: Considering a population-dependent incidence rate, an increase in new cases of PC is expected. This increase is particularly evident in the age groups of 70-74 and 80-84 years. With regards to RT, the estimate indicates an overall increase of 27.4% in demand. There is also a shift in RT demands towards older patients, especially in the 80- to 84-year-old age group. CONCLUSION: We observe an age-associated increase in primary cases of PC. This is likely to result in an increased demand for RT. The exact demand cannot be predicted. However, trends can be estimated to plan for the demand. This, though, requires a good database from cancer registries.

Late radiation sequelae as a consequence of breast-conserving therapy with cobalt irradiation aggravated by various risk factors.

This report deals with a 71-year-old female patient who developed cancer in her right breast 20 years ago, underwent breast-conserving surgery and received normofractionated radiotherapy with a 60Co unit. 19 years later, fibroids and calcified tissue appeared in her right mammary fold. Furthermore, a deep ulceration developed in this region during chemotherapy of bronchial carcinoma. Apart from being a Type 2 diabetic with arterial hypertension, she was also a habitual smoker. After extensive wound debridement and vacuum-assisted sealing therapy, the affected ribs were dissected and a latissimus dorsi flap was implanted. Our focus here is on the interaction of contributing risks for the development of late radiation sequelae, such as physical (especially unintended hot spots during 60Co irradiation) and pathophysiological factors (comorbidities and morbid affections). Fortunately, side-effects such as these are rare nowadays. As this case shows, however, they can be effectively handled by employing modern plastic surgery techniques.

Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

Lymph node positive head and neck carcinoma after curative radiochemotherapy: a long lasting debate on elective post-therapeutic neck dissections comes to a conclusion.

There has been a long lasting debate, whether planned neck dissections after curative radio(chemo)therapy for locally advanced head and neck squamous cell carcinomas offer some benefit in tumor control or survival. We did a thorough literature research on that topic. The results of several recently published studies are described, summarized, and reviewed. Patients with residual disease in clinical or radiographic examinations (CT or MRI scans) up to 3 months after completion of radiochemotherapy profit from neck dissections. In patients with an initial or delayed clinical complete remission after completion of radiochemotherapy, a neck dissection can be safely omitted. In conclusion, there is no longer evidence for a benefit of prophylactic post-radiochemotherapy neck dissections, but strong evidence for a therapeutic post-radiochemotherapy neck dissection in this group of patients.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.

Chemoradioimmunotherapy with 5-fluorouracil, cisplatin and interferon-alpha in pancreatic and periampullary cancer: results of a feasibility study.

BACKGROUND: Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-alpha (IFN-alpha) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. PATIENTS AND METHODS: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n=7) or periampullary (n=4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-alpha was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly. RESULTS: The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. CONCLUSION: Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-alpha and cisplatin as a possible new treatment of pancreatic cancer in resected patients.

Combining radiation with oxaliplatin: a review of experimental results.

Oxaliplatin is integrated in treatment strategies against a variety of cancers including chemoradiation protocols against gastrointestinal, especially rectal cancers. Solid biological data with respect to radiosensitizing activity of oxaliplatin are still rare. This review is based on in vitro and experimental in vivo data concerning the combination of oxaliplatin and radiation published until July 2007. Taking either cell viability or clonogenic survival as an endpoint all reported on oxaliplatin-induced radiosensitization, and enhancement ratios ranged from 1.1 to 2.2. In vivo, enhanced tumor growth delay after combined oxaliplatin and radiation treatment was also reported. Therefore, oxaliplatin should be considered a potent radiosensitizer, although the mechanisms causing radiosensitizing properties of oxaliplatin have not been studied in detail. Herein, they are discussed with respect to apoptosis induction, p53-related signalling, cell cycle control, and DNA-repair.

Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

Presence of human papillomavirus-18 and Epstein-Barr virus in a squamous cell carcinoma of the tongue in a 20-year-old patient. Case report and review of the current literature.

We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus. To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral oncogenesis of oral carcinomas.

Interactions between radiation and endocrine therapy in breast cancer.

Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to patients with invasive breast cancer or with ductal carcinoma in situ (DCIS). Although both therapies have been well established through a number of randomized studies, little is known about a possible interaction of both treatment modalities if they are given simultaneously. A number of in vitro studies have indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of MCF-7 breast cancer cells. Conversely, estradiol treatment increases the intrinsic radiosensitivity of MCF-7 cells. In one available animal study, an antagonistic effect of tamoxifen and ionizing radiation (XRT) could not be observed. Retrospective analyses of randomized clinical studies have not indicated an antagonistic effect of tamoxifen on the effectiveness of XRT, since local control has been consistently higher when XRT was combined with tamoxifen, compared with treatment with XRT alone, regardless of whether tamoxifen was started simultaneously with radiotherapy or after completion of radiotherapy. Currently there are no clinical data available that would suggest an adverse effect of adjuvant tamoxifen treatment started prior to or simultaneously with radiotherapy in breast cancer or DCIS. However, since an antagonistic effect of tamoxifen and simultaneous chemotherapy has been reported recently, the issue of simultaneous versus sequential radiation and tamoxifen treatment in breast cancer should be addressed in further studies.

[The value of qualitative regression grading as a prognostic factor for survival after preoperative radiochemotherapy in patients with advanced head and neck cancer]. / Wertigkeit eines qualitativen Regressionsgradings als prognostischer Faktor für das Uberleben bei präoperativ radiochemotherapierten Patienten mit fortgeschrittenen Kopf-Hals-Karzinomen.

BACKGROUND: Multimodal therapeutic strategies gain importance in locally advanced squamous cell carcinoma of the head and neck. Quantitative regression grading can be traced as an independent prognostic parameter in the histological examination in many neoadjuvantly treated cancers. Various regression systems have been suggested. We propose an easy to apply and economical score that seems to have a significant prognostic value in squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: 43 patients with Stage IV squamous cell carcinoma of the head and neck have been treated neoadjuvantly with two cycles chemotherapy (ifosfamide 1.5 g/m2 day 1-5 with mesna [300 mg/m2], cisplatin 60 mg/m2 day 5, second cycle day 22). Hyperfractionated accelerated radiotherapy (30 Gy) was given from day 29 on. We divided the resected tumors histologically as follows: Grade I--no tumor cells to be identified, Grade II--necrosis, Grade III--partial destruction of the carcinoma, Grade IV--vital carcinoma. RESULTS: After 1 year the overall survival amounted to 79%, after 2 years 56%. A significant correlation could be established between qualitative tumor regression and survival. The 1-year survival depended on the regression of the primary as follows: 94% in Grade I, 80% in Grade II, 60% in Grade III and 56% in Grade IV. For the 2-year survival: 76%, 40%, 40%, 11% (p < 0.01). The results were similar regarding the neck dissections. CONCLUSIONS: After radiochemotherapy the histological regression is a significant prognostic factor of survival. A simple system with four subgroups is suggested which seems to be of a high prognostic value. We discuss to intensify the treatment for patients with good regression after neoadjuvant therapy for a further reduction of recurrence.