Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature

BACKGROUND: Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's wort). CASE REPORT: A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. CONCLUSION: Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative drugs because patients tend to conceal such medication as harmless

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

BACKGROUND: The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. METHODS: From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m(2)/d DDP + 750–1000 mg/m(2)/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. RESULTS: Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. CONCLUSION: The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients were not anemic at beginning of therapy. Therefore, we could assess the influence of pre-treatment hemoglobin on survival. However, a low hemoglobin nadir was associated with poor outcome. This result suggests an influence of anemia during therapy on prognosis

Clinical Results of Intracoronary Brachytherapy (ICBT) for Multiple In-Stent Restenosis

BACKGROUND AND PURPOSE: Treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. PATIENTS AND METHODS: 40 patients (27 male, 13 female, age: 66 +/- 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste((R)) Beta-Cathtrade mark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. RESULTS: The 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). CONCLUSION: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT

Einführung der IMRT zur Therapie kurativ zu behandelnder HNO-Tumoren

Background and Purpose: Intensity modulated radiation therapy (IMRT) is an established technique for the treatment of prostate cancer. Volumetric modulated arc therapy (VMAT) has recently been introduced clinically. Nucletron BV (Veenendal, Netherlands) offers both optimisation algorithms on the same platform in Oncentra® MasterPlan 3.3. Methods: In this planning study five patients with localised prostate cancer are enrolled to compare these two algorithms. The planning target volume (PTV) and the rectum volume, urinary bladder and femoral heads are delineated as organs at risk (OAR). Collimator and table angles are kept fixed during the treatment. The planning is accomplished using the machine data of a SynergyS linear accelarator of the Elekta Company. For the IMRT seven equispaced beams are chosen, starting at a gantry angle of 0°, followed by 51°, 103°, 154°, 206°, 257° and 309°. The VMAT calculations are made based on a dual arc technique rotating from 182° to 178° and back. The dose-volume objectives are kept identical: Planning Target Volume minimum dose 68 Gy, maximum dose 72 Gy, both weighted 3000, urinary bladder 40 Gy to 50% of the volume, weight 1000, rectum 40 Gy to 30% of the volume, weight 1000, and both femoral heads set to a maximum dose of 30 Gy, weight 300. Average doses for the organs at risk and target dose homogeneity H are evaluated.The homogeneity is hereby defined as (D5-D95)/DAV. Furthermore the number of monitor units are compared. For one representative case the treatment times are measured. Results: The results of the dose distribution are rather similar: the average homogeneity for the VMAT plans is 0.088, in IMRT 0.094, both exceed the dose-volume objectives for the rectum (46,1 and 44,7 Gy) and the bladder (43,3 and 44.1 Gy). The objectives for the femoral heads are kept rather well although the weight is low (34,1 and 32,1 Gy). The number of monitor units is clearly higher for the VMAT plans than for the IMRT (1016 and 698 MU). But as the measurement of the treatment times in one representative case (1088 and 775 MU) shows, there is nevertheless an advantage in treatment time for the VMAT case (8,09 min versus 10,14 min). Conclusion: The results of the dose distribution are similar enough that VMAT is an interesting alternative for the treatment of prostate cancer. The treatment time, which is the crucial factor regarding intrafractional organ movements is advantageous for the VMAT technique

Extent of Resection in Newly Diagnosed Glioblastoma: Impact of a Specialized Neuro-Oncology Care Center

Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the implementation of a large technical portfolio including functional imaging, awake craniotomy, PET scanning, fluorescence-guided resection, and integrated postsurgical therapy. This study analyzed whether the technically improved neurosurgical treatment structure yields a higher rate of complete resection, thus ultimately improving patient outcome. Patients and methods: The study included 149 patients treated surgically for newly diagnosed GBM. The neurological performance score (NPS) and the Karnofsky performance score (KPS) were measured before and after resection. The extent of resection (EOR) was volumetrically quantified. Patients were stratified into two subcohorts: treated before (A) and after (B) the foundation of the Regensburg NOC. The EOR and the PFS and OS were evaluated. Results: Prognostic factors for PFS and OS were age, preoperative KPS, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase 1 (IDH1) mutation status and EOR. Patients with volumetrically defined complete resection had significantly better PFS (9.4 vs. 7.8 months; p = 0.042) and OS (18.4 vs. 14.5 months; p = 0.005) than patients with incomplete resection. The frequency of transient or permanent postoperative neurological deficits was not higher after complete resection in both subcohorts. The frequency of complete resection was significantly higher in subcohort B than in subcohort A (68.2% vs. 34.8%; p = 0.007). Accordingly, subcohort B showed significantly longer PFS (8.6 vs. 7.5 months; p = 0.010) and OS (18.7 vs. 12.4 months; p = 0.001). Multivariate Cox regression analysis showed complete resection, age, preoperative KPS, and MGMT promoter status as independent prognostic factors for PFS and OS. Our data show a higher frequency of complete resection in patients with GBM after the establishment of a series of technical developments that resulted in significantly better PFS and OS without increasing surgery-related morbidity

Medical decision-making of the patient in the context of the family: results of a survey

GOALS OF THE STUDY: From the perspective of patient autonomy, the family is often looked upon as a troublemaker in medical decision-making. The question remains open as to whether it is possible to do justice to the autonomy of the individual patient and to the claims of his family at the same time. PATIENTS AND METHODS: A clinical study was undertaken when both patients and dependents were interviewed. One hundred people (50 pairs) participated in this study and could be analyzed. A questionnaire consisting of 15 items was used and was evaluated to see if and how the attitudes concerning medical decision-making differ between patient and dependent. RESULTS: The majority of the interviewees (89%) agreed with the opinion that medical decisions should be made jointly by the patient, the family, and the doctor. Ninety-three percent approved of the claim to inform not only the patient, but also the family. Seventy percent of the patients and 54% of the dependents think that the family is entitled to have a say in matters concerning medical decision-making, only 30% of the patients, but 42% of the dependents argued against this view. Eighty-four percent of the patients argued against a change in this right at the end of life, which was approved by 32% of the family members. CONCLUSIONS: The family plays a central role in medical decision-making. This could be shown by a survey among patients with malignant diseases and their dependents. These initial findings must be verified in a larger population. The increased inclusion of the family in the process of medical decision-making corresponds in general to the expressed will of the patients. The model of shared decision-making is favored by values which both the family and the patient have in common. Thus, a family-based decision-making theory needs to be formulated in the future