Pan-Canadian Analysis of Practice Patterns in Small Cell Carcinoma of the Cervix: Insights from a Multidisciplinary Survey.

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.

Enhancing Nutrition Support for Esophageal Cancer Patients: Understanding Factors Influencing Feeding Tube Utilization.

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.

Clinical Validation of Human Papilloma Virus Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer.

PURPOSE: Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease. METHODS: This prospective, multicenter validation study accrued patients with stage IB-IVA cervical cancer treated with CRT between 2017 and 2022. Participants underwent phlebotomy at baseline, end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT for HPV ctDNA levels. Plasma HPV genotype-specific DNA levels were quantified using both dPCR and HPV-seq. The primary end point was 2-year PFS. RESULTS: With a median follow-up of 2.2 (range, 0.5-5.5) years, there were 24 PFS events among the 70 patients with HPV+ cervical cancer. Patients with detectable HPV ctDNA on dPCR at the end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT had significantly worse 2-year PFS compared with those with undetectable HPV ctDNA (77% v 51%, P = .03; 82% v 15%, P < .001; and 82% v 24%, P < .001, respectively); the median lead time to recurrence was 5.9 months. HPV-seq showed similar results as dPCR. On multivariable analyses, detectable HPV ctDNA on dPCR and HPV-seq remained independently associated with inferior PFS. CONCLUSION: Persistent HPV ctDNA after CRT is independently associated with inferior PFS. HPV ctDNA testing can identify, as early as at the end of CRT, patients at high risk of recurrence for future treatment intensification trials.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators.

PURPOSE: Surface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALS: Planning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3-5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTS: Ten patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7-40.6), mean CTV D0.1cc 49.2 Gy (range 45.6-53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0-1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONS: SMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

High dose rate brachytherapy in the management of anal cancer: A review.

PURPOSE: To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. METHODS AND MATERIALS: A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included. RESULTS: Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively. CONCLUSION: Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.

Changing Landscape of Radiation Therapy for Advanced Cervical Cancer With a Focus on Interstitial Brachytherapy: A Canadian Practice Patterns Survey.

PURPOSE: To document the evolution of radical radiation therapy and interstitial brachytherapy (ISBT) utilization practice patterns across Canada, including use of imaging, technical details, and usage of anesthesia/analgesia, and to compare advanced (AC) versus nonadvanced (nAC) brachytherapy (BT) center practices. METHODS AND MATERIALS: All Canadian centers with BT services were identified. One gynecology radiation oncologist per center was sent a 64-item questionnaire regarding the center's practice for patients with cervical cancer. Centers were categorized based on availability of advanced BT expertise (AC) versus those referring patients to other centers for advanced BT techniques (nAC). Aggregate responses are reported and compared with practice patterns identified in our previous survey. Descriptive statistics were used to summarize data, and the Fisher exact test, Fisher-Freeman-Halton, or Mann-Whitney-Wilcox test was used for comparisons. RESULTS: Thirty-seven of 38 respondents completed the survey (response rate: 97.4%). Compared with 2015, there has been an increase in utilization of magnetic resonance imaging as the sole imaging modality for BT planning: 3 of 26 (11%) versus 12 of 37 (32%; P = .03). The number of centers with the ability to perform ISBT increased in 2020 compared with 2015 (26/37 [70%] vs 13/26 [50%], P = .710); this trend is likely due to an increase in use of hybrid (Vienna, Utrecht, Venezia) applicators (36% [2015] vs 84% [2020]; P = .175). Fifteen (40%) centers had the ability to perform perineal-ISBT (P-ISBT). Sixteen and 21 centers were identified as AC and nAC, respectively. All 16 AC centers had the ability to perform ISBT, compared with only 10 nAC centers (P < .001). A higher proportion of AC centers had fellowship-trained radiation oncologists performing brachytherapy, compared with nAC centers (94% vs 14%, P < .001). In terms of anesthesia, conscious sedation was the only available choice at low-patient-volume centers (8/37, 21%) performing intracavitary BT only. Those performing ISBT had choice of general, spinal, and epidural anesthesia. CONCLUSIONS: In Canada, high-quality, modern management radiation therapy practices are consistently offered to patients with cervical cancer. There is a trend toward increased utilization of ISBT. Accumulation of evidence toward the use of ISBT, increased utilization of high-quality imaging modalities such as magnetic resonance imaging, and availability of hybrid applicators are potential contributors for this upward trend.

A systematic review of intraluminal high dose rate brachytherapy in the management of malignant biliary tract obstruction and cholangiocarcinoma.

PURPOSE: To conduct a systematic review evaluating the impact of high dose rate (HDR) intraluminal brachytherapy (ILBT) in the management of malignant biliary obstruction and cholangiocarcinoma with specific focus on stent patency, clinical outcomes and toxicities. METHODS AND MATERIALS: A review of published articles was conducted using Medline, Embase and Cochrane databases using the search terms "bile duct carcinoma" or "cholangiocarcinoma" or "bile duct neoplasms" in combination with "brachytherapy" or "high dose rate brachytherapy" or "HDR brachytherapy". Studies published in English and reporting outcomes of ≥10 patients were included in the review. Only the most recent experience was included if same patients were included in sequential publications. RESULTS: Seventeen studies were identified that met the inclusion criteria. Significant heterogeneity was observed in treatment regimens, which included use of surgery, external beam radiation (EBRT), and/or intra-arterial and intravenous chemotherapy in conjunction with ILBT. Nevertheless, among the included studies, use of ILBT appeared to result in longer duration of stent patency: 10 months with ILBT compared to 4-6 months without ILBT. A trend was observed towards prolonged local control and improved complete and partial response rates in patients treated with ILBT with or without EBRT. Weighted mean overall survival of patients treated with ILBT alone was 11.8 months compared to 10.5 months for those that received EBRT +/- chemotherapy in addition to ILBT. The included studies reported low complication rates and toxicity related to ILBT. CONCLUSION: Brachytherapy can be an effective and safe tool in the management of malignant biliary tract obstruction in combination with stenting. Both retrospective and prospective studies have suggested improved outcomes when HDR ILBT is combined with percutaneous stenting.

Acute and late complications and toxicities of skin brachytherapy.

Skin cancer is the most prevalent malignancy, and its incidence is rising. Surgery is the primary treatment, however, morbidity of surgical resection in certain parts of the body warrant alternate treatment options such as radiation therapy. Complex topology of the skin can pose a challenge for treatment with photon and electron external beam radiotherapy techniques. Brachytherapy can be an attractive radiotherapy technique for these regions. Furthermore, brachytherapy results in lower dose to the underlying deep organs. The goal of this manuscript is to provide a brief overview of the role of brachytherapy for skin malignancies and to outline potential acute and long-term toxicities.

Substantial lymphovascular space invasion predicts worse outcomes in early-stage endometrioid endometrial cancer.

INTRODUCTION: Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. METHODS AND MATERIALS: Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan-Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. RESULTS: In total, 325 patients were identified with a median follow-up of 35 (23-48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57-94)%, focal LVSI 89 (79-100)%, and no LVSI 94 (90-98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0-51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2-16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2-25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7-11.4); p = 0.002] predicted for worse disease-free survival. DISCUSSION: Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.

Salvage surgery for locally recurrent anal cancer after intensity modulated radiation therapy with concurrent chemotherapy.

INTRODUCTION: Chemoradiation (CRT) with intensity modulated radiation treatment (IMRT) has become the standard for anal cancer. In patients who fail this treatment modality, salvage surgery with abdominal perineal resection can result in long term cancer control. We aimed to evaluate a single centre's experience of salvage surgery for local recurrence since the introduction of IMRT. MATERIALS AND METHODS: A retrospective chart review was performed of all patients who underwent definitive CRT for anal carcinoma at a single tertiary referral center since IMRT became standard in 2009. Patients with recurrent or persistent disease after treatment who underwent salvage surgery were included. Details of CRT, salvage surgery and surgical complications, patterns of recurrence after surgery, and survival data were collected and described. RESULTS: Between 2009-2018, 181 patients underwent definitive treatment using IMRT for anal carcinoma. Of 26 patients who had locoregional recurrent or persistent disease, 14 underwent salvage surgery. Nine had multi-visceral resection and 8 required autologous flap reconstruction. Twelve patients had resections with clear margins and 2 had microscopic positive margins. Twelve patients (86%) experienced post-operative complications, and eight (57%) had perineal wound complications. After salvage, four patients (29%) recurred locally. None of the 8 patients with rpT2 disease recurred. After salvage surgery, 5-year disease free survival was 68.4% and 5-year overall survival was 75%. CONCLUSION: Following IMRT based chemoradiation, salvage surgery has high rates of surgical complications; however disease free and overall survival results are excellent particularly for small recurrences.

Exposure to radiation and medical oncology training: A survey of Canadian urology residents and fellows.

INTRODUCTION: Residency experiences and teaching in oncology among urology residents are variable across Canada. We sought to identify how radiation and medical oncology concepts, as they pertain to genitourinary malignancies, are taught to urology residents. METHODS: A total of 190 trainees enrolled in Canadian urology residency training programs were invited to participate in the study from January 2016 to June 2016. Participants completed an online questionnaire addressing the training they received. RESULTS: The overall response rate was 32%. Twenty-three percent of respondents were in their fellowship year; 17%, 20%, 10%, 17%, and 12% were first-, second-, third-, fourth-, and fifth-year residents, respectively, with a median of four (range 1-9) respondents from each training program. Ninety-five percent of respondents had academic half-day (AHD) as part of their training that included radiotherapy (61%) and chemotherapy (51%) teaching. Most respondents indicated their main exposure to chemotherapy and radiation came from informal teaching in urology clinics. Twenty-nine percent and 41%, of participants had mandatory rotations in radiation and medical oncology, respectively. Only 6% of respondents used their voluntary elective time in these disciplines and most voluntary electives were of 1-2-week duration. Despite this, 90% of respondents preferred some mandatory radiation and medical oncology training. CONCLUSIONS: Most of the limited exposure that urology residents have to medical and radiation oncology is through AHD or informal urology clinics, despite a desire among current urology trainees to have clinical exposure in these areas. Moving forward, urology residency programs should consider integrating medical and radiation oncology rotations into the residency program curriculum.

Endoluminal high-dose-rate brachytherapy for locally recurrent or persistent esophageal cancer.

PURPOSE: Management of locally recurrent or persistent esophageal cancer (EC) after standard chemoradiation is challenging. This study updates our experience of treating medically inoperable EC patients with endoluminal high-dose-rate brachytherapy (EHDRBT) including the patients treated with a novel multiballoon channel centering esophageal applicator. METHODS AND MATERIALS: Thirty-three consecutive patients with early-stage primary (n = 7), posttreatment persistent (n = 7), and recurrent (n = 19) EC treated with EHDRBT at our institution were included. Median dose and treatment lengths were 14 Gy (range 10-17.5 Gy) and 6 cm (3.5-9.0 cm), respectively. Endoscopy and biopsy were performed 3 months after EHDRBT and then every 3-6 months thereafter. RESULTS: Median followup was 17.4 months (range 5.0-88.3). Grade 1 and 2 toxicities were observed in 13 (44.8%) and 11 (37.9%) patients, respectively. Grade 3 toxicity (tracheoesophageal fistula) was observed in 1 patient who had previously received two courses of external beam radiotherapy as well as a stent insertion. Median overall survival (OS) for entire cohort was 20.9 months, and 1-year OS was 78%. Complete response was achieved in 58.6% of patients with median time to failure and 1-year disease-free survival of 10.3 months (range 5.4-28.2) and 27%, respectively. CONCLUSIONS: For medically inoperable patients with early-stage primary or local posttreatment residual or recurrent EC, EHDRBT is a well-tolerated treatment option with minimal Grade ≥3 toxicity. Brachytherapy in our hands continues to be a safe treatment option. Although 58.6% of patients achieved a complete response and the OS of this cohort is relatively good, long-term local control and cure remains a challenge.

Volumetric-modulated arc therapy versus intensity-modulated radiotherapy for large volume retroperitoneal sarcomas: A comparative analysis of dosimetric and treatment delivery parameters.

PURPOSE: To compare dosimetric and treatment delivery parameter differences between volumetric-modulated arc radiotherapy (VMAT) and intensity-modulated radiotherapy (IMRT) for large volume retroperitoneal sarcomas (RPS). MATERIALS AND METHODS: Both VMAT and IMRT planning were performed on CT datasets of 10 patients with RPS who had been previously treated with preoperative radiotherapy. Plans were optimized to deliver ≥95% dose to the PTV and were evaluated for conformity and homogeneity. Dose to the organs at risk (OARs) (kidney, liver, spinal cord, and bowel space), unspecified tissue, and dose evaluation volumes (DEVs) at 1, 2, and 5 cm from PTV were calculated and compared. Monitor units (MUs) and treatment delivery times were recorded and compared between the two techniques. The deliverability of the large volume RPS VMAT plans was verified by portal dosimetry on a Truebeam™ linac. RESULTS: VMAT and IMRT plans were equivalent for PTV coverage and homogeneity (P > 0.05); however, VMAT plans had slightly better conformity index, CI (P < 0.001). Doses to the OARs were not significantly different between VMAT and IMRT plans (P > 0.05). Mean doses to the unspecified tissue as well as at 1, 2, and 5 cm DEVs were lower with VMAT compared with IMRT, P = 0.04 and P < 0.01, respectively. MUs and average beam-on times were both significantly lower in the VMAT vs IMRT plans, P < 0.001 and P = 0.001, respectively. All VMAT plans passed portal dosimetry delivery verification with an average gamma passing rate of 99.6 ± 0.4%. CONCLUSIONS: VMAT planning for large volume RPS improved CI, and achieved comparable OAR sparing, as compared with IMRT. As treatment delivery time was lower, the use of VMAT for RPS may translate into improved treatment delivery efficiency.

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103.

PURPOSE: Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity. METHODS AND MATERIALS: Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance). RESULTS: On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V100%), dose to 1 cc of rectum (D1cc), and dose to 2 cc of rectum (D2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V100 and dose to 90% of gland (D90) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D20, D5cc, and D1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity-6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding. CONCLUSIONS: Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.

Intraoperative implantation of a mesh of directional palladium sources (CivaSheet): Dosimetry verification, clinical commissioning, dose specification, and preliminary experience.

PURPOSE: To present the clinical commissioning of a novel 103Pd directional brachytherapy device (CivaSheet) for intraoperative radiation therapy. METHODS AND MATERIALS: Clinical commissioning for the CivaSheet consisted of establishing: (1) source strength calibration capabilities, (2) experimental verification of TG-43 dosimetry parameters, (3) treatment planning system validation, and (4) departmental practice for dose specification and source ordering. Experimental verification was performed in water with radiochromic film calibrated with a 37 kVp X-ray beam. Percentage difference ([measurements - calculation]/calculation) and distance to agreement (difference between film-to-source distance and distance that minimized the percentage difference) were calculated. Nomogram values (in U/100 Gy) for all configurations (up to 20 × 20 sources) were calculated for source ordering. Clinical commissioning was used on patients enrolled in an ongoing Institutional Review Board-approved protocol. RESULTS: A source calibration procedure was established, and the treatment planning system was commissioned within standard clinical uncertainties. Percentage dose differences (distances to agreement) between measured and calculated doses were 8.6% (-0.12 mm), 0.6% (-0.01 mm), -6.4% (0.22 mm), and -10.0% (0.44 mm) at depths of 2.3, 5.1, 8.0, and 11.1 mm, respectively. All differences were within the experimental uncertainties. Nomogram values depended on sheet size and spatial extent. A value of 2.4U/100 Gy per CivaDot was found to satisfy most cases, ranging from 2.3 to 3.3U/100 Gy. Nomogram results depended on elongation of the treatment area with a higher variation observed for smaller treatment areas. Postimplantation dose evaluation was feasible. CONCLUSIONS: Commissioning and clinical deployment of CivaSheet was feasible using BrachyVision for postoperative dose evaluation. Experimental verification confirmed that the available TG-43 dosimetry parameters are accurate for clinical use.

Real-time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program.

PURPOSE: Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program. METHODS AND MATERIALS: Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed. RESULTS: When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%. CONCLUSIONS: In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce intraoperative errors and chances for suboptimal dose delivery during prostate brachytherapy.

Cervical cancer brachytherapy in Canada: A focus on interstitial brachytherapy utilization.

PURPOSE: Brachytherapy (BT) techniques for cervical cancer in Canada have changed over the last decade, with evolution to high-dose-rate and image-guided BT. However, there are currently no national data on the use of interstitial BT (IBT). The purpose of this study was to document IBT utilization in Canadian centers, as well as update details of cervical cancer BT practices. METHODS AND MATERIALS: All Canadian centers with gynecologic BT services (n = 33) were identified, and one gynecology radiation oncologist per center was sent a 33-item e-mail questionnaire regarding their center's practice for cervical cancer BT in 2015. Responses were reported and compared with practice patterns identified in a 2012 Canadian survey. RESULTS: The response rate was 85% (28/33 centers). The majority (93%) of respondents used high-dose-rate BT, similar to the 2012 survey; 96% of centers had transitioned to three-dimensional (MRI/CT)-based planning in 2015 vs. 75% in 2012 (p = 0.03); 57% centers incorporated MRI for treatment planning in 2015 compared to 38% in 2012 (p = 0.15); the majority (13/16) using a combination of MRI and CT; 50% (14/28 centers) had the capacity to perform IBT, whereas 71% of those that did not referred patients to other centers. Of centers performing IBT, the majority (11/14) used template-based techniques with a median of 6 (range 2-20) needles/catheters and an average of 4 (range 1-5) fractions. Catheters were placed using: strategy based on pre-op imaging (21%), intra-op ultrasound (50%), intra-op MRI (7%), and intra-op CT (21%). The most common dose/fractionation schedules were 6 Gy × 5 fractions (40%), 8 Gy × 3 fractions (19%), and 7 Gy × 4 fractions (15%). CONCLUSIONS: In Canada, treatment of cervical cancer continues to evolve. IBT has been adopted by half of the responding centers. As more centers move to MRI-based image-guided treatment planning, IBT will become an even more integral part of cervical cancer treatment.

Secondary Neuroendocrine Carcinoma Following High-Dose Radiotherapy for Head and Neck Cancer: Report of Two Cases.

Patients treated with radiation have an increased risk of developing second cancers, of which carcinomas, sarcomas, and hematological malignancies have most commonly been reported. Neuroendocrine carcinomas (NEC) are rarely reported in patients previously treated with radiation. Two patients, who had successfully undergone chemoradiotherapy for head and neck cancers at our institution, developed secondary NEC within the radiation field more than five years after the treatment. Both patients underwent curative-intent treatment of secondary malignancies, one with chemotherapy, radiation and surgery (Case 1) and the other with chemotherapy and surgery (Case 2). Both had no evidence of disease at a short follow-up of twelve months (Case 1), and three months (Case 2) after treatment. NEC can develop post-radiotherapy; a multidisciplinary approach is necessary to successfully treat these patients.

Copper-topotecan complexation mediates drug accumulation into liposomes.

These studies describe the role of transition metal ions in the liposomal encapsulation of topotecan. Liposomes (1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol (CH) (55:45, mole ratio)) were prepared with manganese (Mn), copper (Cu), zinc (Zn) or cobalt (Co) ion gradients (metal inside). Subsequently, topotecan was added to the liposome exterior (final drug-to-lipid ratio (mol/mol) of 0.2) and drug encapsulation was measured as a function of time and temperature. No drug loading was achieved with liposomes containing Co or Zn. Topotecan could be encapsulated into Mn-containing liposomes only in the presence of the ionophore, A23187 suggesting that a transmembrane pH gradient was necessary. However, Cu-containing liposomes, in the presence or absence of an imposed pH gradient, efficiently encapsulated topotecan. It has been reported that Cu(II) can form transition metal complexes with camptothecin; therefore, the Cu-topotecan interaction was characterized in solution as a function of pH. These investigations demonstrated that topotecan inhibited formation of an insoluble Cu hydroxide precipitate. Cryo-TEM analysis of the topotecan-loaded Cu liposomes showed electron-dense intravesicular precipitates. Further studies demonstrated that only the active lactone form of the drug was encapsulated and this form predominated in Cu-containing liposomes. Copper complexation reactions define a viable methodology to prepare liposomal camptothecin formulations.