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The purpose of this study was to evaluate the effect of a lead block for alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer.We treated 6 patients and delivered 5,400 cGy in 9 fractions using a lead block. Effects of lead block (median thickness, 4 mm) on dose attenuation by distance were visually examined using TG-43 formalism-based dose distribution curves to determine whether or not the area with the highest dose is located in the alveolar bone, where there is a high-risk of infection. Dose re-calculations were performed using TG-186 formalism with advanced collapsed cone engine (ACE) for inhomogeneity correction set to cortical bone density for the whole mandible and alveolar bone, water density for clinical target volume (CTV), air density for outside body and lead density, and silastic density for lead block and its' silicon replica, respectively.The highest dose was detected outside the alveolar bone in five of the six cases. For dose-volume histogram analysis, median minimum doses delivered per fraction to the 0.1 cmThe results suggested that using a lead block for alveolar bone protection with a thickness of about 4 mm, can shift the highest dose area to non-alveolar regions. In addition, it reduced D0.1cm

This study compares the effect of iodinated contrast agent on Hounsfield unit (HU)-based TG-186 dose calculation vs. delivered dose for high-dose-rate (HDR) iridium-192 brachytherapy using a phantom model.A reservoir filled with a diluted contrast agent was placed inside a water phantom. A single steel needle applicator was centrally positioned inside the reservoir. Computed tomography (CT) datasets of five different contrast agent dilutions (25 to 300 mg/ml iodine concentration) were acquired, and dose calculations were performed with TG-186 ACE dose calculation formalism of OncentraFor the different contrast agent dilutions, averaged Hounsfield units from 453 ±21 to 2623 ±221 were obtained. Electron densities derived from CT data were significantly higher than corresponding electron densities calculated from chemical compositions. Consequently, the measured dose was higher than corresponding HU-based calculated dose. Relative deviation ranged from 2.5% to 7% per 10 mm penetration depth, depending on contrast agent concentration.The application of HU-based TG-186 dose formalisms in the presence of high-Z contrast agent bulks overestimates electron densities. Consequently, HU-based dose calculations result in a higher delivered dose than expected from the treatment planning system.

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa. ispartof: Int J Radiat Oncol Biol Phys vol:116 issue:3 pages:503-520 ispartof: location:United States status: published

Epidemiological data indicate that more than 50 % of patients with newly-diagnosed rectal cancer are older than 70 years, with rising numbers expected over the next decades. Treatment decision-making is challenging in elderly and frail patients with rectal cancer, whereas standardized treatment guidelines for this patient cohort are lacking. Elderly and frail rectal cancer patients are often considered by surgeons as unfit to undergo radical surgery as the risk of surgical complications and postoperative mortality rises with increasing age and comorbidity. Furthermore, these patients often receive no treatment at all, resulting in local and/or systemic disease progression with associated symptoms and impaired quality of life (QoL). Recent data from randomized trials in young fit patients with early stage rectal cancer indicate that RT dose escalation can be safely delivered using external beam (chemo)radiotherapy (EBRT) followed by endoluminal radiotherapeutic modalities, such as contact X-ray brachytherapy (CXB) or high-dose rate endorectal brachytherapy (HDR-BT). However, prospective studies testing this therapeutic concept in elderly and frail patients remain limited. Here, we review the current evidence in the epidemiology and the management of elderly and frail patients with rectal cancer. We summarize the potential of RT dose escalation to achieve long-term local control of the primary tumour, prevent disease-related morbidity, improve QoL and even organ preservation. Future perspectives and open questions will be discussed as well.

Purpose High-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) are currently the two treatment options for definitive radiotherapy of prostate cancer, employing extreme hypofractionation. There are only very few studies comparing their dosimetry, all using computed tomography for treatment planning. We present here a real-word dosimetric comparison between SBRT and ultrasound-based virtual HDR-BRT, with both imaging modalities coming from the same patient. Methods and Materials Patients with prostate cancer on a prospective trial evaluating the toxicity of robotic-based SBRT were treated to a total dose of 35 Gy in 5 fractions. Fifteen patients were included in this analysis. During ultrasound-based fiducial implantation, a three-dimensional data set as in real HDR-BRT procedure was acquired. Virtual HDR-BRT plans were generated and various organs at risk and prostate dosimetric parameters were evaluated. Results Concerning prostate, SBRT achieved significant higher D98, V35 Gy, and V37.5 Gy coverage, whereas virtual HDR-BRT achieved significant higher intratumoral doses reflected in the V42 Gy and V52.5 Gy. Rectal Dmax, V36 Gy, and V29 Gy were significantly lower for HDR-BRT with no difference as for V18 Gy. SBRT was significantly inferior regarding bladder dosimetry (Dmax, V36 Gy, V18 Gy), whereas urethra Dmax and V44 Gy where significantly higher at the expense of HDR-BRT. Conclusions HDR-BRT is superior regarding rectum and bladder dosimetry, with SBRT being superior relative to urethra dosimetry. A randomized study is warranted to define the best extreme hypofractionated modality.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D 90 , D 98 , and D 100 of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D2cc values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.

Purpose As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. Methods Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1‑3, N0‑1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10–13 × 3 Gy EBRT followed by HDR-BT delivering 12–18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. Results Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8–60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. Conclusion Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.

Baseline uptake on prostate-specific membrane antigen (PSMA)-targeted imaging is a prerequisite for radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. This study aims to quantify lesion-based response to RLT in relation to pretreatment standard molecular imaging metrics derived from [68Ga]Ga-PSMA-11 PET/CT. Sixty-one patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging before and after a median of 4 (IQR 2–6) RLT cycles. Maximum and mean standardized uptake values (SUVmax, SUVmean), as well as tumor-to-liver ratio (TLR), were assessed. A median of 12 (IQR 7–17) lesions was analyzed per patient, resulting in a total of 718 lesions. Lesions with ≥30% SUVmax decline or falling below the blood pool uptake were considered responsive; ≥30% SUVmax increase marked lesion progression. Additionally, 4-point visual scoring was performed according to E-PSMA consensus. In total, 550/718 (76.6%) lesions responded to RLT, including 389/507 (76.7%) bone metastases and 143/181 (79.0%) lymph node metastases. Baseline SUVmax, SUVmean, and TLR values were associated with lesion response by a moderate but significant correlation (rs = 0.33, p < 0.001, rs = 0.32, p < 0.001, and rs = 0.31, p < 0.001, respectively). For the classification of lesion progression based on baseline PSMA uptake, receiver operating characteristics (ROC) found SUVmax, SUVmean, and TLR to have comparable discriminatory value (AUC 0.85, 0.87, and 0.83). Of 42 tumor sites with baseline uptake below the liver (V-score < 2), 19/42 (45.2%) were responsive, 9/42 (21.4%) were stable, and 14/42 (33.3%) showed progression, leaving liver uptake a threshold with low prognostic value for the identification of RLT-refractory lesions (PPV 33%). This was observed accordingly for various liver uptake-based thresholds, including TLR < 1.5

Purpose: Tongue edema is a potential cause of treatment target underdosage in high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To prevent such edema-associated alteration of dosimetry, we developed a special silicon device. In this report we communicate our initial experience with two mobile tongue cancer patients whom we treated using this new device. Material and methods: The device consists of silicone tubes with a fixed width and scalable length depending on tongue size. These tubes are lined and fixed like a palisade, allowing the device to be used also as a template. The device is placed next to the lateral border of the tongue and on the floor of the mouth. In addition, a vinyl template can be placed on the dorsal tongue surface with both devices combined for implantation guidance. Between June and August 2012, two patients with locally confined tongue cancer were treated. Results: Between June and August 2012, two mobile tongue cancer patients classified as cT2N0M0 were treated with HDR-ISBT using the silicone device. They underwent ISBT as monotherapy with fractional doses of 6.0 Gy up to a total physical dose of 54.0 Gy. The D90 (CTV) values of both patients were 6.3 Gy and 6.6 Gy and the D2cc (mandible) values were 3.4 Gy and 2.6 Gy, respectively. At present, both patients remain without local disease recurrence at 60 and 56 months after ISBT, respectively. Conclusions: The described silicone device has the potential to prevent underdosage to the treatment target related to tongue edema. It has been shown to be safe and easy to implement.

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose–volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18–1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours.

Purpose The purpose of this study was to report our initial experience of hyaluronic acid gel injection (HGI) in the vesicovaginal septum (VVS) for bladder dose reduction in brachytherapy (BT) for uterine cervical carcinoma. Material and methods Between September 2016 and May 2018, 15 uterine cervical cancer patients received HGI in the VVS as a part of their definitive radiotherapy (RT) treatment consisting of external beam radiation therapy (EBRT) with additional BT. Of those, 9 patients received BT both with and without HGI, and remaining 6 patients were excluded because these 6 patients received HGI in the VVS for all BT fractions. All 9 patients received HGI in the rectovaginal septum. For these patients, the dosimetric parameters bladder D2cc, HR-CTV D90, and rectum D2cc were selected, and two groups were generated (BT with vs. without HGI in the VVS) for dosimetric comparison. Results The median cumulative EQD2 for HR-CTV, rectum D2cc, and bladder D2cc for the 9 patients were 73.3, 52.8, and 67.1, respectively. While no statistical difference could be detected for rectal dose reduction, bladder dose was significantly less in the group with HGI in the VVS compared to that without (449 cGy [range, 416-566, 1SD = 66.1] vs. 569 cGy [range, 449-647, 1SD = 59.5], p = 0.033), with no compromising of target coverage. Although it did not reach statistically significance, there was a trend toward better HR-CTV D90 in the group with HGI compared to that without HGI in the VVS (713 cGy vs. 706 cGy, p = 0.085). No severe bleeding, hematuria, bladder wall injury, or urethral injury requiring hospitalization was experienced in association with HGI in the VVS. Conclusions HGI in the VVS can be performed safely and can effectively reduce the bladder dose in BT for uterine cervical cancer patients.

We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.

To compare dosimetrically the radiation exposure to heart, left ventricle (LV), and left anterior descending artery (LAD) between whole-breast radiotherapy (WBRT) with Active Breathing Coordinator (ABC; ABC-WBRT) and interstitial multicatheter high-dose-rate (HDR) brachytherapy as accelerated partial breast irradiation (ABPI; imHDR-APBI) for left-sided breast cancer (BCA) after breast-conserving surgery (BCS). Between January 2016 and December 2019, 32 and 20 patients were treated with ABC-WBRT (63 Gy/2.25 Gy) and imHDR-APBI (32 Gy/4 Gy), respectively. Among them a matched-pair analysis was performed according to tumor location (clock position) before BCS as well as planning target volume of imHDR-APBI and boost volume of ABC-WBRT. This yielded 17 pairs of patients for whom dosimetric parameters for heart, LV, and LAD were evaluated. The Mann–Whitney test was used for comparison after adjusting for equivalent dose in 2‑Gy fractions (EQD2). In addition, a second analysis of ABC-WBRT to 40.05 Gy in 15 fractions was performed in order to account for the EQD2 difference between the 63-Gy ABC-WBRT and the imHDR-APBI protocol. Tumor location for the 17 pairs of patients relative to breast quadrant was as follows: upper outer 8, lower outer 5, upper inner 3, and lower inner 1. There was no difference regarding mean heart dose (MHD) and V5, whereas D25%, D45%, V10, and V25 significantly favored imHDR-APBI. Likewise, mean dose- and V5-LV did not differ, while Dmax- and V23-LV were significantly higher for ABC-WBRT. For LAD, Dmax, D25%, and V30 significantly favored imHDR-APBI without differences for mean dose and V40. When comparing imHDR-APBI with the 40.05 Gy ABC-WBRT schedule, MHD and mean dose LV were significantly lower in favor of ABC-WBRT. ABC-WBRT and imHDR-APBI yield similar low heart and LV exposure for left-sided BCA after BCS, whereas LAD can be better spared with imHDR-APBI.

This study aimed to determine the efficacy and safety of robotic-based fractionated stereotactic radiotherapy (FSRT) in the treatment of large brainstem metastases (BSMs).Ten BSM were treated in ten patients with FSRT between January 2012 and December 2018. The median age was 61 years (range, 53-74 years) with a median Karnofsky Performance Score of 80 (range, 70-90). Four patients (40%) had received whole-brain radiotherapy prior to FSRT. The median tumor volume was 4.2 cmRobotic-based FSRT for BSM appears to be safe with favorable LC and low toxicity even for large tumors.

An innovative template, based on thoracic cage surface reconstructions for breast interstitial brachytherapy was developed. Hybrid-inverse-planning-optimisation-based implantations and brachytherapy plans, using three custom anthropomorphic breast phantoms, were utilised for its validation. A user independent, inverse planning and inverse implanting technique is proposed.

Purpose To report the clinical outcomes and treatment-related toxicities after combined high-dose-rate (HDR) brachytherapy (BRT) with external beam radiotherapy (EBRT) for patients with clinically localised high-risk prostate cancer. Material and methods Between 2008 and 2012, three hundred and three consecutive patients with organ-confined high-risk prostate cancer were treated with definitive radiotherapy consisting of HDR-BRT followed by supplemental EBRT. The transrectal 3D-ultrasound-based HDR-BRT boost consisted of two single-fraction implants of 10.5 Gy, prescribed to the 90% of the gland (D90), for a total physical dose of 21.0 Gy delivered to the prostatic gland. EBRT was delivered with conventional fractionation, prescribing 45.0 Gy to the prostatic gland and seminal vesicles. Biochemical failure was defined according to the Phoenix Consensus Criteria, genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated using the Common Toxicity Criteria for Adverse Events (version 3.0). Results The median follow-up was 71.6 months. The 7-year overall survival, biochemical control and metastasis-free-survival rates for the entire cohort were 85.7%, 88.3% and 93.8%, respectively. Androgen deprivation therapy was initiated prior to treatment for 92.7% of patients with a median duration of 12 months. Toxicity was scored per event with late Grade 2, 3 and 4 GU adverse events and was found to be 15.3%, 2.2% and 0.3%, respectively. Late Grade 2 GI toxicity accounted for 0.3% with no instances of Grade 3 or higher late adverse events. Conclusion HDR-BRT with supplemental EBRT results in low biochemical relapse-free survival rates associated with a very low incidence of higher-grade late adverse events.

Purpose The aim of this study was to investigate the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (ISBT) for reirradiation of locally recurrent uterine cervical cancer. Methods and Materials Between 2008 and 2015, patients receiving reirradiation using HDR-ISBT for local gross recurrence of uterine cervical cancer after definitive or postoperative radiotherapy were analyzed retrospectively. The prescription doses per fraction ranged 2.5–6.0 Gy, whereas the cumulative equivalent doses in 2 Gy fractions ranged 48.6–82.5 Gy. The effects of prognostic factors on the local control (LC), progression-free survival, and overall survival were analyzed, and late toxicity data were evaluated. Results Eighteen patients were included in the analysis, with a median followup of 18.1 months. A tumor response was obtained in all patients, with radiological and pathological complete remission seen in 12 (66.7%) patients. The 2-year LC, progression-free survival, and overall survival rates for all patients were 51.3%, 20.0%, and 60.8%, respectively. The hemoglobin level and maximum tumor diameter were shown to be statistically significant prognostic factors for LC (p = 0.028 and 0.009, respectively). Late ≥ Grade 2 adverse events were observed in 5 patients (27.8%). Conclusions Image-guided HDR-ISBT for the reirradiation of locally recurrent uterine cervical cancer may play an important role for local tumor control in a subgroup of patients. However, the treatment indication must be weighed against the risk of higher-grade late toxicity.

Background and purpose To evaluate the oncological outcome of a three-implant high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically localised prostate cancer. Material and methods Between February 2008 and December 2012, 450 consecutive patients with clinically localised prostate cancer were treated with HDR monotherapy. The cohort comprised of 198 low-, 135 intermediate- and 117 high risk patients being treated with three single-fraction implants of 11.5 Gy delivered to an intraoperative real-time, transrectal ultrasound defined planning treatment volume up to a total physical dose of 34.5 Gy with an interfractional interval of 21 days. Fifty-eight patients (12.8%) received ADT, 32 of whom were high- and 26 intermediate-risk. Biochemical failure was defined according to the Phoenix Consensus Criteria and genitourinary/gastrointestinal toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.0. Results The median follow-up time was 56.3 months. The 60-month overall survival, biochemical control and metastasis-free-survival rates were 96.2%, 95.0% and 99.0%, respectively. Toxicity was scored per event with late Grade 2 and 3 genitourinary adverse events of 14.2% and 0.8%, respectively. Late Grade 2 gastrointestinal toxicity amounted 0.4% with no instances of Grade 3 or greater late adverse events to be reported. Conclusions Our results confirm HDR BRT to be a safe and effective monotherapeutic treatment modality for clinically localised prostate cancer.

Purpose: When squamous cell carcinoma of the buccal mucosa (BSCC) extends surrounding anatomical sites such as gingiva, retromolar triangle, or hard palate, it might be challenging to ensure adequate tumor coverage by sole interstitial brachytherapy due to the complexity of catheter implantation. By combining interstitial catheters with an enoral placed, individually assembled “oral spacer plus embedded catheters” device (hybrid of intracavitary-interstitial brachytherapy), it should be easier to deliver the necessary tumoricidal dose to irregular-shaped tumor volumes (clinical target volume – CTV) with improved conformity. The purpose of this analysis was to compare the dose distribution created by the hybrid of intracavitary-interstitial brachytherapy (HBT) with the dose distribution of an interstitial catheter only-approach, based on the interstitial catheters used for HBT (ISBT-only) by evaluating respective treatment plans (HBT plan vs. ISBT-only plan) for the treatment of early stage BSCC. Material and methods: A retrospective analysis was performed for patients with localized BSCC treated between April 2013 and October 2017. All patients received sole HBT without additional external beam radiation therapy or planned neck dissection. Dosimetric parameters taken into account for comparison between actual HBT and virtual ISBT-only were CTV D90, CTV V100, CTV V150, CTV V200, mandible D2cc, and mucosal surface D2cc. Results: Dosimetrically, HBT showed a trend toward better CTV D90 compared to ISBT-only. In addition, HBT demonstrated statistically better CTV V100 coverage compared to ISBT-only. There was no statistically significant difference with respect to CTV V150, CTV V200, and mucosal surface D2cc, while a trend was seen in better mandible D0.1cc between HBT and ISBT-only. Conclusions: The HBT approach appears to enable improved dose coverage of irregular-shaped enoral tumor volumes compared to ISBT-only for patients with early stage BSCC.

The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81-93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0-16% and 0-2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.

Purpose Intratarget dose escalation with superior conformity is a defining feature of three-dimensional (3D) iridium-192 ( 192 Ir) high-dose-rate (HDR) brachytherapy (BRT). In this study, we analyzed the dosimetric characteristics of interstitial 192 Ir HDR BRT for intrathoracic and cerebral malignancies. We examined the dose gradient sharpness of HDR BRT compared with that of linear accelerator–based stereotactic radiosurgery and stereotactic body radiation therapy, usually called X-Knife, to demonstrate that it may as well be called a Knife. Methods and Materials Treatment plans for 10 patients with recurrent glioblastoma multiforme or intrathoracic malignancies, five of each entity, treated with X-Knife (stereotactic radiosurgery for glioblastoma multiforme and stereotactic body radiation therapy for intrathoracic malignancies) were replanned for simulated HDR BRT. For 3D BRT planning, we used identical structure sets and dose prescription as for the X-Knife planning. The indices for qualitative treatment plan analysis encompassed planning target volume coverage, conformity, dose falloff gradient, and the maximum dose–volume limits to different organs at risk. Results Volume coverage in HDR plans was comparable to that calculated for X-Knife plans with no statistically significant difference in terms of conformity. The dose falloff gradient—sharpness—of the HDR plans was considerably steeper compared with the X-Knife plans. Conclusions Both 3D 192 Ir HDR BRT and X-Knife are effective means for intratarget dose escalation with HDR BRT achieving at least equal conformity and a steeper dose falloff at the target volume margin. In this sense, it can reasonably be argued that 3D 192 Ir HDR BRT deserves also to be called a Knife, namely Iridium-Knife.

To review the current status of interstitial high-dose-rate brachytherapy as a salvage modality (sHDR BRT) for locally recurrent prostate cancer after definitive radiotherapy (RT). A literature search was performed in PubMed using “high-dose-rate, brachytherapy, prostate cancer, salvage” as search terms. In all, 51 search results published between 2000 and 2016 were identified. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control (BC) and toxicity scores. Eleven publications reported clinical outcome and toxicity with follow-up ranging from 4–191 months. A variety of dose and fractionation schedules were described, including 19.0 Gy in 2 fractions up to 42.0 Gy in 6 fractions. The 5‑year BC ranged from 18–77%. Late grade 3 genitourinary and gastrointestinal toxicity was 0–32% and 0–5.1%, respectively. sHDR BRT appears as safe and effective salvage modality for the reirradiation of locally recurrent prostate cancer after definitive RT.

Introduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT. Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset. Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses. Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.

Background Locally advanced uterine cervical cancer (LAUCC) with lateral tumor extension may not always be covered adequately by conventional intracavitary brachytherapy (ICBT). Hybrid intracavitary and interstitial brachytherapy (HBT) seems to be an effective alternative by improving anatomy-oriented dose optimisation. The purpose of this study was to report initial clinical result for LAUCC treated by HBT. Methods Between January 2012 and November 2015, 42 patients with LAUCC (T1b2-4a) were treated with primary radiation therapy including HBT. Patients with distant metastasis other than para-aortic lymph node spread were excluded from this study. A retrospective analysis was performed for toxicity evaluation and oncological outcome calculation. Results Median follow-up was 23.2 months (range 13.2–71.4). Two-year overall survival, progression free survival, and local control rate were 81.6, 54.4, and 80.2%, respectively. Seven patients experienced local recurrence (16.6%). Of those, five were confined to the uterus and two at the parametria. Late adverse events ≥ grade 3 were seen in 3 patients. Conclusions HBT can generate favorable local control in tumors which cannot be adequately covered by ICBT.

Purpose To report our results of image-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the primary treatment of patients with inoperable glioblastoma multiforme (GBM) in the pre-temozolomide period. Material and methods Between 1994 and 2004, 17 patients were treated with HDR BRT for inoperable GBM. Of those, only 11 patients were treated with IRT BRT, and the remaining six patients received combined IRT BRT and external beam radiotherapy (EBRT). Patient's median age was 59.3 years (range, 29-83 years) and median tumor volume was 39.3 cm3 (range, 2-162 cm3). The prescribed HDR dose was median 40 Gy (range, 30-40 Gy), delivered twice daily in 5.0 Gy fractions over four consecutive days. Survival from BRT, toxicity as well as the impact of several prognostic factors was evaluated. Results At a median follow-up of 9.3 months, the median overall survival for the whole population, after BRT alone, and combined BRT with EBRT was 9.3, 7.3, and 10.1 months, respectively. Of the prognostic variables evaluated in univariate analysis, i.e., age, Karnofsky performance score, BRT dose, and tumor volume, only the latter one reached statistical significance. Two patients (11.7%) developed treatment-associated adverse events, with one (5.8%) symptomatic radionecrosis and one (5.8%) severe convulsion episode, respectively. Conclusions For patients with inoperable GBM, IRT HDR BRT alone or in combination with EBRT is a safe and effective irradiation method providing palliation without excessive toxicity.

Highlights • Conventional fractionated radiotherapy (RT) is predominantly used for the palliation of symptomatic metastatic disease. • Hypofractionated stereotactic RT is increasingly adopted for the treatment of locally recurrent and oligometastatic disease. • High-dose radiation seems to have an immunogenic effect in patients with renal cell cancer. • Combinations of ablative RT with immunotherapies are promising approaches that might improve outcomes., Purpose To review the role of radiotherapy (RT) in the treatment of renal cell cancer (RCC) in the curative and palliative setting. Content Details related to the clinical outcomes of primary, preoperative, postoperative and palliative RT are discussed, along with a presentation of the established role of surgery and systemic therapy. An overview of data derived from mono- and multi-institutional trials is provided. Conclusion Radiotherapy has been shown to provide good symptom palliation and local control in RCC depending on the dose that can be delivered. There is emerging data suggesting that with the use of high-precision RT methods the indication spectrum of RT can be exploited covering different clinical situations particularly for unresectable local recurrences and oligometastatic disease.

To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient’s median age was 57.1 years (14–82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2–207 cm3). The prescribed HDR dose was median 40 Gy (30–50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.

Glioblastoma multiforme patients presenting with recurrence following multimodality therapy have limited palliative treatment options when the major modalities of therapy including surgery, radiochemotherapy and adjuvant chemotherapy have been exhausted. The authors introduce a clinical and radiological indication-solving algorithm and provide outcome rates of a glioblastoma recurrence cohort. Sixty six consecutive adult patients with recurrent glioblastoma who underwent a combined scheme of salvage treatments consisting of reoperation, high dose rate (HDR) brachytherapy and chemotherapy were included in this prospective study and were compared to a historical control group of 24 recurrent glioblastoma patients who have been treated with intensive temozolomide chemotherapy as the only treatment modality. Median follow-up was 32 months (range 28-36 months). Median survival was 9 months for the entire cohort after salvage treatment and can be translated into a 3-month improvement in survival compared to the control group of patients with glioblastoma recurrence treated with temozolomide alone (P = 0.043). Toxicity and adverse events of reoperation, HDR brachytherapy combined with chemotherapy were quite favourable compared to intensive temomozolomide chemotherapy as the only treatment. Our experience suggests that a combined salvage treatment plan appears to be both feasible and effective and can be considered in selected patients affected by recurrent high grade gliomas. The authors' clinical and radiological indication-solving algorithm may assist in providing the best possible salvage treatment for this difficult population.

Purpose To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

Radiation therapy (RT) comprises a key component in the treatment of breast cancer. Radiation-induced skin toxicity is the major adverse event experienced by patients; however, radiodermatitis (RD) prevention and management remains trivial. It is proven that photobiomodulation (PBM) therapy using light-emitting diode (LED) increases wound healing and depicts an anti-inflammatory effect. This single-institute study evaluates the beneficial role of PBM-LED in preventing/reducing RD during breast cancer RT. Of 70 consecutively treated patients, 25 patients were treated with PBM-LED twice a week prior to adjuvant 3D conformal RT after breast-conserving surgery. RD was reported using Common Toxicity Criteria for Adverse Events Version 4.0 and pain intensity using a visual analog scale (VAS). For comparison, a control group (n = 45) received RT without PBM-LED. In addition, a “matched” group (n = 25) was generated from the control group based on propensity for potentially confounding variables. In the PBM group, 22 patients (88%) presented grade 1 and 3 (12%) grade 2 RD. In the control group, 25 patients (55.6%) developed grade 1 reactions, 18 patients (40%) grade 2, and 2 (4.4%) patients grade 3 RD. Concerning pain intensity, 15 patients (60%) of the PBM treatment arm reported no pain, 5 patients (20%) VAS 2, and 5 (20%) VAS 3. In the control group, 13 patients (28.9%) reported no pain, 2 (4.4%) VAS 1, 7 (15.6%) VAS 2, 9 patients (20%) reported VAS 3, 12 (26.7%) patients VAS 4, and 2 (4.4%) patients VAS 5. PBM-LED therapy applied prior to RT might be effective in decreasing the incidence and sequelae of radiation-induced skin toxicity in breast cancer patients treated with breast-conserving surgery.

Radiation recall dermatitis (RRD) refers to an acute inflammatory skin reaction appearing on a previously irradiated area following the systemic administration of a reaction-triggering agent. Despite various hypotheses, the pathomechanism of RRD appears complex and is still not fully understood. In addition, no clinical guidelines exist concerning whether drug treatment should be continued upon manifestation of an associated radiation recall phenomenon. We present the case of a patient with docetaxel-induced RRD, which was successfully treated with topical steroids and systemic antihistamines; re-challenge to docetaxel did result in very mild remanifestation of skin reactions.

High-dose rate brachytherapy for prostate cancer has enjoyed rapid acceptance and is one of the most active areas of clinical research in the field. We present this chapter as a comprehensive technical analysis of rationale, methods, and outcomes including a substantive data review.

The Gorham–Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide. A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization. Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40–45 Gy are recommended.

Background Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC. Patients and methods From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0–36.0 Gy) in twice-daily fractions of 2.0–5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0–36.0 Gy) in once-daily fractions of 6.0–10.0 Gy in three patients. Results The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III–IV complications occurred in 13% of patients. Conclusions In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control.

Recurrences of glioblastoma multiforme (GBM) within previously irradiated volumes pose a serious therapeutic challenge. This retrospective study evaluates the long-term tumor control of recurrent GBM treated with interstitial high-dose-rate brachytherapy (HDR-BRT).Between 1995 and 2003, 84 patients were treated for recurrent cerebral GBM located within previously irradiated volumes. All patients had received adjuvant external radiotherapy following primary surgery, with a focal dose up to 60 Gy. The median recurrent tumor volume was 51 cm(3) (3-207 cm(3)), and the HDR-BRT consisted of an afterloading (192)Ir implant which delivered a median dose of 40 Gy (30-50 Gy). Catheter implantation was implemented using interactive computed tomography (CT) guidance under local anesthesia and sedoanalgesia.After a median follow-up of 61 months, 5/84 patients (6%) were alive. The median post-BRT survival was 37 weeks, and the median overall survival 78 weeks. Moderate to severe complications occurred in 5/84 cases (6%).For patients with recurrences of GBM within previously irradiated volumes, CT-guided interstitial HDR-BRT is a feasible treatment option that can play an important role in providing palliation.

To compare the 4th edition 1992 and 6th edition 2002 of the American Joint Committee on Cancer (AJCC) staging systems, to evaluate the paranasopharyngeal structures and lymph node involvement, and to define the prognostic significance of the above factors to overall survival (OS) in patients with locally advanced nasopharyngeal carcinoma (NPC). CT images of 162 patients, who were diagnosed with NPC and received irradiation alone or chemotherapy and irradiation, were retrospectively reviewed. CT scans, performed prior to and after the completion of treatment, were reviewed. The parapharyngeal space was found to be involved very commonly (98%). 50 of 162 patients (31%) displayed parapharyngeal extension of the tumor to degree A, 59 patients (36%) showed degree B, and 50 patients (31%) degree C nasopharyngeal extension. According to the AJCC 6th edition 2002, patients were distributed into stages IIA, IIB, III, IVA, and IVB. By contrast, using the AJCC 4th edition 1992, patients were distributed into stages III and IV only. After a median follow up of 71.1 months, median survival was 60.7 months, with a 2-year survival rate of 71.3% and a 3-year survival rate of 62.2%. Multivariate analysis identified age, degree of parapharyngeal lateral extension, cavernous-sinus-infiltration, and size of infiltrated lymph nodes as independent prognostic factors for OS. The 6th revision of TNM staging reported herein, provides a more uniform distribution of patients between stages. The degree of tumor extension into the parapharyngeal space should be considered in future TNM staging revisions

Case report A 32-year-old female patient underwent surgical synovectomy in the right distal radioulnar joint because of local recurrence of pigmented villonodular synovitis (PVNS) after previous surgery. 7 weeks after her second surgery she received fractionated radiation therapy (RT) to a total dose of 36.0 Gy given in five weekly fractions of 2.0 Gy. Apart from a mild skin erythema the patient had no early morbidity related to the use of RT. After a follow-up of 36 months no local recurrence was detected. Conclusion In accordance with literature data the hitherto course of the presented case corroborates that RT is a safe and effective treatment option for the prevention of PVNS recurrence.

Purpose: We present the largest study of both peripheral blood and lymph node samples examining the utility of reverse transcription-polymerase chain reaction (RT-PCR) for established molecular markers as a diagnostic tool in the molecular staging of prostate cancer patients undergoing radical prostatectomy. Experimental Design: Peripheral blood from 358 patients was obtained before radical prostatectomy. Corresponding obturatory lymph node samples were collected from 153 of these patients. Nested RT-PCR for prostate-specific antigen (PSA), human kallikrein 2 (hK2), and prostate-specific membrane antigen (PSMA) were performed on cDNA from peripheral blood. The lymph node cDNA was analyzed for PSA und hK2 expression. Results: RT-PCR in peripheral blood was positive in 124 (34.6%) of 358 samples for PSA, 215 (60.1%) of 358 for PSMA, and 97 (27.1%) of 358 for hK2. Comparison of positive RT-PCR rates of pT2 and pT3 tumors in corresponding peripheral blood for PSA, PSMA, and hK2 were 31.9 and 40.0%, 58.8 and 62.5%, and 26.9 and 27.5%, respectively. Histopathologically, cancer-free lymph node samples were positive in RT-PCR for PSA and hK2 in 70 (49.6%) of 141 and 89 (63.2%) of 141 of cases. All histologically positive lymph node samples (n = 12, pN+) were positive for PSA RT-PCR. PSA RT-PCR alone, as well as combined PSA/PSMA RT-PCR evaluation, in peripheral blood showed a significant association with grading. PSA RT-PCR lymph node-negative samples were significantly less likely positive in their corresponding peripheral blood RT-PCR sample. Conclusions Although the preoperative PSA RT-PCR in peripheral blood correlated with the grading of prostate cancer, no combination of RT-PCR results using “triple” markers (PSA, hK2, PSMA) in peripheral blood and/or lymph nodes yielded additional preoperative staging information.

Purpose To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. Methods and materials A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. Results The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% ± 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% ± 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. Conclusions Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

To report the methods and clinical results of CT-based interstitial high-dose-rate (HDR) brachytherapy procedures for the palliative treatment of recurrent rectal cancer. Patients and Methods: A total of 44 brachytherapy implants were performed in 38 patients. CT-guided catheter implants were performed in 34 patients under local anesthesia and sedation, and four patients were implanted intraoperatively. Of 40 CT-guided implants, 20 were done using metallic needles introduced via the sacrum and 20 were transperineal implants of plastic tubes in the presacral region. Postimplant CT scans were used for three-dimensional (3-D) conformal brachytherapy planning. Patients implanted with metallic needles were given a single fraction of 10–15 Gy using HDR 192Ir, and those who received transperineal implants of plastic catheters were given fractionated brachytherapy, 5 Gy twice daily to a total dose of 30–40 Gy. The median tumor volume was 225 cm3 with a range of 41–2,103 cm3. Results: After a median follow-up of 23.4 months, a total of 13/38 patients were alive. The median postbrachytherapy survival was 15 months with 18 of the 25 deaths due to distant metastases. Tumor response was as follows: 6/38 partial remission, 28/38 stable disease, and 4/38 local progression. A planning target volume (PTV) coverage > 85% was achieved in 42/44 implants. The treatment was well tolerated, and no acute complications were observed. One patient developed a fistula after 8 months. Pain relief was recorded in 34 patients (89.5%), and the median duration of this palliative effect was 5 months with a range of 1–13 months. Conclusions: Interstitial HDR brachytherapy is a valuable tool for the delivery of high doses and achieves effective palliation in recurrent rectal carcinoma.

Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P (+)), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 x 20 Gy, 98.6% in 2 x 14 Gy, 97.5% in 3 x 11 Gy, and 97.8% in 4 x 9.5 Gy. The corresponding P+ values were 88.8% in 1 x 20 Gy, 83.9% in 2 x 14 Gy, 86.0% in 3 x 11 Gy, and 82.3% in 4 x 9.5 Gy. With use of the fractionation scheme 4 x 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 x 19.68 Gy, 2 x 13.75 Gy, and 3 x 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 x 19.16 Gy with a P+ of 91.8%, 2 x 13.2 Gy with a P+ of 89.6%, 3 x 10.6 Gy with a P+ of 88.4%, and 4 x 9.02 Gy with a P+ of 86.9%. Conclusions: Among the fractionation schemes 1 (+) 20 Gy, 2 (+) 14 Gy, 3 x 11 Gy, and 4 x 9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 x 9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.

Objectives Tumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy. Design Retropective cohort study. Setting Primary level of care with two participating centres. The geographical location was central Germany. Participants From January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression. Interventions This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. Primary and secondary outcome measures Median survival, progression free survival and complication rate. Results Median survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p

Purpose To report our results of computed tomography (CT)–guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the local treatment of inoperable primary and secondary liver malignancies. Methods and Materials Between 2000 and 2009, 31 patients underwent a total of 42 BRT procedures for 36 hepatic lesions exceeding 4 cm and located adjacent to the liver hilum and bile duct bifurcation. The median tumor volume was 99 cm 3 (range, 46–1348 cm 3 ). The median age was 64 years (range, 27–85 years). The HDR-BRT delivered a median total physical dose of 13.0 Gy (range, 7.0–32.0 Gy) in twice daily fractions of median 7.0 Gy (range, 4.0–10.0 Gy) in 14 patients and in once daily fractions of median 8.0 Gy (range, 7.0–14.0 Gy) in 17 patients. Results The median followup was 13.3 months with an overall survival rate of 66% at 1 year. The local control rate for patients with metastatic lesions was 79%, 59%, and 59%, and for the subgroup with primary hepatic tumors 88%, 50%, and 50% at 1, 2, and 3 years, respectively. Severe side effects occurred in 4.7% of BRT procedures with no treatment-related deaths. Conclusions Our results confirm CT–guided interstitial HDR-BRT to be a safe procedure for the local treatment of inoperable liver malignancies unsuitable for thermal ablation.

Bisphosphonate (BP) use has increased dramatically in recent years, becoming an integral part of the overall antineoplastic management of patients with metastatic bone disease. Even though their application has shown to be effective in reducing pain and minimizing the risk of skeletal-related events, their administration may bring also adverse events such osteonecrosis of the jaws (ONJ). After a thorough review of the literature, important aspects of the pathophysiology, diagnosis, prevention, and treatment of ONJ are presented. ONJ is evident in up to 10% of patients receiving intravenous BP treatment. Despite the fact that its exact pathophysiology is unknown, it is characterized by bone necrosis that can occur either spontaneously or after dental surgery or tooth extraction. Panoramic radiographs are useful for the diagnosis and routine assessment of patients and computed tomography can differentiate between ONJ and metastatic disease. Additionally, magnetic resonance imaging depicts local disease extension readily, and scintigraphy is the most sensitive imaging modality for detecting early involvement. Preventive measures and routine dental evaluations are essential components of the overall patient management. In the event of ONJ, stage I or II should be managed conservatively, whereas more advanced stages (III and IV) should be treated surgically. ONJ is a well-defined clinical entity that all medical and dental doctors should be aware of, since if it is not dealt with readily and effectively, it may deteriorate the clinical status and quality of life of affected patients.

The importance of tumor volume as a prognostic factor in high-grade gliomas is highly controversial and there are numerous methods estimating this parameter. In this study, a computer-based application was used in order to assess tumor volume from hard copies and a survival analysis was conducted in order to evaluate the prognostic significance of preoperative volumetric data in patients harboring glioblastomas. 50 patients suffering from glioblastoma were analyzed retrospectively. Tumor volume was determined by the various geometric models as well as by an own specialized software (Volumio). Age, performance status, type of excision, and tumor location were also included in the multivariate analysis. The spheroid and rectangular models overestimated tumor volume, while the ellipsoid model offered the best approximation. Volume failed to attain any statistical significance in prognosis, while age and performance status confirmed their importance in progression-free and overall survival of patients. Geometric models provide a rough approximation of tumor volume and should not be used, as accurate determination of size is of paramount importance in order to draw safe conclusions in oncology. Although the significance of volumetry was not disclosed, further studies are definitely required.

Nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. A total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection.