Prior External Beam Radiation Research Articles

Brachytherapy in the Management of Esophageal Cancer: A Single Institution Experience

Esophageal brachytherapy has been shown to be effective in palliating dysphagia. This treatment enables delivery of a high dose of radiation therapy (RT) to the tumor whereas dose is limited to nearby organs, which allow its use in salvage after a prior external beam RT. Despite known efficacy and available guidelines, brachytherapy remains underutilized. This study evaluates the practice of brachytherapy, symptomatic response to this treatment, and observed toxicities at a single center. A literature review was carried out to identify and review the articles related to brachytherapy in management of esophageal cancer. A retrospective chart review was conducted after identifying 28 patients who received esophageal brachytherapy at our center from 2009-2017. A review of medical records provided information about their diagnosis, management, and follow-up. Descriptive statistics were utilized along with Kaplan and Meier method for time to event variables. The usual brachytherapy dose was 18 Gy in 3 fractions over 1-2 weeks and the external beam RT dose used was 50 Gy in 25 fractions over 5 weeks. Mellow and Pinkas dysphagia scoring system was used to assess swallowing. Most (71.4%) patients were male. Approximately two thirds of patients had an adenocarcinoma located in the lower thoracic esophagus. Majority (68%) received brachytherapy for persistent dysphagia with a palliative intent. Eight (29%) patients received brachytherapy after developing a local failure post curative intent treatment for salvage. One patient received curative intent brachytherapy in combination with EBRT. A majority (56%) of patients had an improvement in swallowing following brachytherapy. The median dysphagia free survival after intraluminal brachytherapy was 13.6 weeks (CI 5.2-21.9). A proportion of patients did not respond where reasons were multifactorial. The observed complication rate was favorable. Only 2 (7%) patients developed strictures requiring dilatation and 3 (10.6%) had bleeding that was controlled. There were no esophageal perforations, development of tracheoesophageal fistulas or mortality associated with brachytherapy. Two patients were lost to follow up. Of the remaining 26 patients, 4 (15.4%) are alive and 22 (84.6%) have died. Literature review supports the use of this modality. Esophageal brachytherapy was fairly well tolerated with an improvement in swallowing by at least one point for most patients. There were no major adverse events. It remains an effective treatment among cases where options are limited such as a local recurrence after an initial curative intent therapy, as well as for relief of dysphagia in a palliative setting. This review found esophageal brachytherapy as an effective and safe management modality. There is a need of an increase in the use of intraluminal brachytherapy and an exposure of radiation oncology trainees to gain technical expertise in its administration.

A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy (NRG Oncology/RTOG-0526)

Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancerbefore EBRT and biopsy-proven recurrence >30months after EBRT, with prostate-specific antigen levels <10ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24months after brachytherapy. These AEs were projected to be ≤10%, with ≥20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs. One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54months (range, 4-97) and a median age of 70years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74Gy (IQR, 70-76) at a median interval of 85months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P=.03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P=.02). This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.

OA170] Myelosuppression in non–hodgkin lymphoma patients treated with 177Lu-lilotomab satetraxetan can be predicted by a model with red marrow absorbed dose as the only parameter

Purpose 177Lu-lilotomab satetraxetan is an antibody-radionuclide conjugate therapy for non–Hodgkin lymphoma, which is currently in a phase 1/2-study. The primary toxicity is transient myelosuppression. The aim of this work was to determine if a linear model including red marrow absorbed dose and various clinical factors can be used to predict myelosuppression. Methods Patient characteristics and dosimetric data for 17 patients were included. All patients had no or minor bone marrow infiltration. The percentage reduction of neutrophils and platelets at nadir compared to baseline was used as to indicate myelosuppression. Platelets and neutrophils were analysed separately. The Common Terminology Criteria version 4.0 were used to grade thrombocytopenia and neutropenia. A total of six factors believed to affect bone marrow reserve were tested: Red marrow absorbed dose, age at treatment, baseline cell-counts, history of prior external beam radiation therapy, total number of previous chemotherapy treatments (including rituximab) and elapsed time since the last chemotherapy treatment. Predictors were found using ordinary least square fitting, testing all possible subsets of variables. A significance level of 0.05 was used. A leave 1-out analysis was used to validate the final model. Results The typical patient, as described by the mean and standard deviation, was 69 (+/−10) years of age at treatment, had previously been treated 2.8 (+/−1.8) times with chemotherapy and might have previously received external beam radiation therapy (5/17 patients). Elapsed time since the last chemotherapy was 20.9 (+/−17.2) months. Mean red marrow absorbed dose was 1.45 (+/−0.45) Gy. Of the sub-sets of predictors investigated, only a model consisting solely of the red marrow absorbed dose was significant (p = 0.048 for platelets and 0.027 for neutrophils). Model coefficients indicate total loss of both platelets and neutrophils at 3 Gy. The leave-1 out analysis resulted in correct prediction of CTCAE-grading +/−1 grade for 76.5 % (13/17) and 88.2 % (15/17) of the patients for thrombocytopenia and neutropenia, respectively. Conclusions A linear model with red marrow absorbed dose as the only parameter predicted myelosuppression in 177Lu-lilotomab satetraxetan treated patients.

The role of salvage brachytherapy for local relapse after external beam radiotherapy for prostate cancer.

Prostate cancer is the most prevalent cancer amongst men. For localized disease, there currently exist several reliable treatment modalities including surgery, radiotherapy and brachytherapy. Our growing understanding of this disease indicates that local control plays a very important role in prevention of subsequent dissemination. Many improvements to external beam radiotherapy over recent years have decreased toxicity and improved outcomes, but nonetheless, local relapse remains common. Many salvage options exist for locally recurrent prostate cancer, but are rarely offered, partly because of the fear of toxicity. Many men with isolated local recurrence therefore do not receive potentially curative second line treatment and are instead treated with palliative androgen suppression. Selection plays an important role in determining which individuals are likely to benefit from salvage. Those at high risk of pre-existing micro-metastatic disease despite negative staging scans are unlikely to benefit. Prostate brachytherapy has evolved over the more than 3 decades of experience. Modern techniques allow more precise tumor localization and dose delivery. Better understanding of dosimetric parameters can distinguish optimal from suboptimal implants. Salvage brachytherapy can be an effective treatment for locally recurrent prostate cancer after prior external beam radiotherapy. We review the literature pertaining to both low dose rate (LDR) and high dose rate (HDR) salvage brachytherapy and discuss patient selection, optimal dose, treatment volume and toxicity avoidance.

Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose–Response for Late Toxicity

Todocument the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16Gy (range, 12-24Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8months (range, 4.2-59.0months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3)>200Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/β ratio of 2]>130Gy) was associated with grade ≥2 late toxicity (P=.036). Maximum point BED3 > 110Gy (or EQD22Gy>70Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P=.017). Nine VCFs (18%) occurred at a median time of 10.2months (range, 3.2-57.2months), with 5- and 10-year VCF rates of 17% and 17%, respectively. Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200Gy and spinal cord or cauda equina point BED3 > 110Gy. Patients remain at moderate risk of VCF up to 5years after treatment, with a plateau in incidence thereafter up to 10years.

Stereotactic body radiotherapy as salvage treatment for recurrence of non-small cell lung cancer after prior surgery or radiotherapy.

Treatment options for thoracic recurrences of non-small cell lung cancer (NSCLC) are limited. Stereotactic body radiation therapy (SBRT) is an emerging, potentially effective technology to manage recurrent NSCLC, although with limited prospective studies. This work reviews the outcomes of patients undergoing salvage SBRT for pulmonary recurrences after prior resection or prior radiotherapy for NSCLC. Following salvage SBRT, after prior external beam radiation (SBRT or conventionally fractionated), the 2-year overall survival (OS) ranged from 37% to 79% in 11 of the studies (397 patients) reviewed here, while the 2-year local control (LC) ranged from 37% to 90% in 6 studies that reported that outcome. Toxicity risks are acceptable albeit with appreciable risks of severe to potentially fatal toxicity, necessitating the need to weigh risks vs. benefits in the re-irradiation setting. There were fewer studies on the use of SBRT after prior resection. Following salvage SBRT, after prior resection, the 2-year OS ranged from 56% to 68% in 4 studies (131 patients) reviewed here, while the 2-year LC ranged from 83% to 100% in 3 of these studies. SBRT in the salvage setting after prior resection appeared to be well-tolerated, with toxicity risks comparable to historical patients treated with SBRT alone (i.e., SBRT without prior resection, which is not reviewed here). The data are limited due to the retrospective nature of published studies (all but 4 with <40 patients), with various clinical scenarios (i.e., original NSCLC stage, prior treatment, location of target amenable to salvage SBRT) and a range of SBRT dosing and techniques. More studies are needed to better understand the tumor control, survival and toxicity of SBRT for salvage therapy of NSCLC patients, as well as the potentially prognostic factors that could affect these outcomes.

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer

AimsRobotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. Materials and methodsData from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. ResultsAll patients received prior EBRT. The median EQD2 total dose was 74 Gy (60–80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of –77.1% (14.3–99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0–2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. ConclusionFocal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.

HDR Interstitial Brachytherapy in the Management of Lip Malignancies

Brachytherapy is an appealing alternative to external beam radiotherapy in the management of early stage primary lip cancers. Historically LDR brachytherapy and recent HDR brachytherapy has been shown to provide at least equivalent local control and improvement in the therapeutic ratio compared to external beam radiation. We report our department experience over the last 3 years. Since 2013, HDR interstitial brachytherapy has been offered to patients with squamous cell carcinoma involving the non-hair bearing lip. It has been offered as monotherapy in the definitive setting for early stage lesions as well as adjuvant therapy in post-operative patients with known pathologic risk factors (+ margins, + PNI) or as a boost after external beam radiotherapy in locally advanced patients requiring nodal irradiation. Since April 2013 through December 2016, 17 patients with Tis-T2 N0 M0 SCCA have been treated with interstitial brachytherapy. 14 patient patients were treated with definitive radiotherapy. 10 of those patients received brachytherapy has monotherapy, while 4 others received external beam radiotherapy followed by a brachytherapy boost. 1 patient received brachytherapy for a recurrence after prior external beam radiation and surgical salvage for recurrence. 2 patients received it as adjuvant therapy after primary surgical resection for known pathologic risk factor of PNI. Brachytherapy dose was 42.5-47.5 Gy in 10 fractions given BID over 1 week in the setting of definitive monotherapy, 17-24 Gy in 5-6 fractions given BID in the setting of a boost after external beam radiation and 35-36 Gy in 9-10 fractions given BID over 1 week in the setting of post-surgical adjuvant therapy for microscopic disease. The median time to follow-up for this cohort is 18 months (3-38 months). The local control rate is 94.1%. There has been one local failure which was then salvaged with single agent Cetuximab. There has been one regional failure along the path of ipsilateral CN V3 which was then treated with chemoradiation. There have been no nodal failures. HDR Interstitial brachytherapy is an excellent radiotherapeutic option for early stage lip SCCA. It offers a very convenient alternative to patients with early stage disease allowing their treatment time to be condensed to 1 week in lieu of a 6-7 week course of external beam radiation.

A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer after External Beam Radiation Therapy (NRG/RTOG0526): Initial Report of Late Toxicity Outcome

Prior studies of low dose rate (LDR) prostate brachytherapy (BT) for salvage of local recurrence (LR) after external beam radiotherapy (EBRT) are limited by retrospective reporting. The primary objective of this prospective Phase II trial (NCT00450411) was to evaluate late gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) after salvage LDR BT. Eligible patients had low or intermediate risk prostate cancer prior to EBRT and biopsy-proven LR >30 mos after EBRT, with PSA < 10 ng/mL and no regional or distant disease. Prescribed minimum target dose was 140 Gy with I-125, or 120 Gy with Pd-103. The primary endpoint was late GI/GU AEs occurring 9-24 mos after BT, Grade 3 or higher, and possibly, probably or definitely attributed to BT. These were projected to be < 10%, with > 20% considered unacceptable. With one-sided significance of 0.05 and 85% power, 87 evaluable patients were required under Fleming’s multiple testing procedure. Analyzable patients had a minimum 23 mos follow-up. All events were graded with CTCAE V3.0. Multivariate analyses sought associations of pre-treatment or treatment variables with AEs. Time to first occurrence of an AE was modelled by the Fine-Gray method. From 05/11/2007 to 01/21/2014, 100 patients were registered from 20 centers, of which 92 were analyzable. Median follow-up was 54 mos (range 4-97); median age 70 (IQR: 65-74). Initial Gleason score was 7 in 48%, and PSA >10 ng/ml in 16%. Median dose of EBRT was 74 Gy (IQR: 70-76). Androgen deprivation was combined with salvage BT in 16%. Median interval from prior EBRT was 85 mos (IQR: 60-119). The primary endpoint was evaluable in 87(95%) of the 92 patients. Twelve (14%) experienced late grade 3 GI/GU AEs (1 proctitis; 1 urethral fistula; the remainder being urinary frequency, incontinence, and retention). There were no treatment-related grade 4 or 5 AEs. No pre-treatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher BT dose predicted both occurrence of late AE (OR 1.24: 95% CI 1.01-1.52; P = 0.04) and time to occurrence (HR 1.19: 95% CI 1.02-1.38; P = 0.03). Although median V150 (% ETV receiving >150% of prescribed dose) was 50%, the range was 18-90%. This is the first prospective multicenter trial to report outcomes of salvage LDR BT for post EBRT LR. The rate of late grade 3 AEs (14%) was not unacceptable by the predetermined protocol specification, without any grade 4-5 events, comparable to a study of primary EBRT + LDR (WR Lee 2007; RTOG 0019). The only factor predictive of late AEs was implant dose, underlining the need for meticulous planning and technique to limit the final delivered dose. Clinical outcomes for efficacy will be reported when minimum 5-yr follow-up is met.

Persistent Hematologic Dysfunction after Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE: Incidence, Course, and Predicting Factors in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent hematologic dysfunction (PHD) after PRRT with 177Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Methods: The incidence and course of PHD were analyzed in 274 GEP NET patients from a group of 367 patients with somatostatin receptor-positive tumors. PHD was defined as diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/MPN, or otherwise unexplained cytopenia (for >6 mo). Using data from The Netherlands Cancer Registry, the expected number of hematopoietic neoplasms (MDS, AML, MPN, and MDS/MPN) was calculated and adjusted for sex, age, and follow-up period. The following risk factors were assessed: sex, age over 70 y, bone metastasis, prior chemotherapy, prior external-beam radiotherapy, uptake on the [111In-DTPA0]octreotide scan, tumor load, grade 3-4 hematologic toxicity during treatment, estimated absorbed BM dose, elevated plasma chromogranin A level, baseline blood counts, and renal function. Results: Eleven (4%) of the 274 patients had PHD after treatment with 177Lu-DOTATATE: 8 patients (2.9%) developed a hematopoietic neoplasm (4 MDS, 1 AML, 1 MPN, and 2 MDS/MPN) and 3 patients (1.1%) developed BM failure characterized by cytopenia and BM aplasia. The median latency period at diagnosis (or first suspicion of a PHD) was 41 mo (range, 15-84 mo). The expected number of hematopoietic neoplasms based on The Netherlands Cancer Registry data was 3.0, resulting in a relative risk of 2.7 (95% confidence interval, 0.7-10.0). No risk factors for PHD could be identified for the GEP NET patients, not even bone metastasis or estimated BM dose. Seven patients with PHD developed anemia in combination with a rise in mean corpuscular volume. Conclusion: The prevalence of PHD after PRRT with 177Lu-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.

Evaluation of outcomes after stereotactic radiosurgery for pilocytic astrocytoma.

Pilocytic astrocytomas are rare intracranial gliomas that are typically treated with surgical extirpation. Our aim was to report the radiologic and clinical outcomes of patients treated with stereotactic radiosurgery (SRS) for pilocytic astrocytoma in the primary and salvage setting. Patients with pilocytic astrocytoma treated at a single institution with SRS from 1990 to 2015 were reviewed. Patient, disease, and treatment characteristics were collected and overall survival, local control, and toxicity were evaluated. Twenty-eight consecutive patients (12 females and 16 males) with a median age of 17.4 years at SRS were identified. Overall, 46% of patients were treated with SRS as part of the initial treatment course after biopsy or subtotal resection, and the remainder as a salvage therapy. The most common location was the cerebellum (28%) followed by brainstem and basal ganglia (21 and 18%, respectively). Four patients received prior external beam radiation therapy (14%). Median tumor volume was 1.84cc (0.19-15.94cc), and 39% had a cystic component at SRS. Prescription dose ranged from 4 to 20Gy (median 16Gy) to a median isodose line of 50% (range 30-100%). With a median follow-up of 5.2 years (0.3-17.1 years), all patients remained alive at last follow-up. Two patients demonstrated evidence of local radiographic progression at last follow-up (7%). No toxicity could be directly attributed to SRS. In this SRS series, durable tumor control was achieved in 93% of patients with pilocytic astrocytoma, although continued follow up will be important giving the natural history of this disease. As demonstrated, SRS is an appropriate technique in the primary and recurrent treatment of pilocytic astrocytoma that offers favorable disease control and infrequent clinical toxicity.

Endobronchial brachytherapy for metastasis from extrapulmonary malignancies as an effective treatment for palliation of symptoms

PurposeEndobronchial metastasis (EBM) originating from primary cancers outside the lung is rare. External beam radiotherapy is often attempted for control of symptoms with variable effectiveness and retreatment is challenging if symptoms recur. There is limited documentation of high-dose-rate brachytherapy for EBM in the literature. Methods and MaterialsA prospective database was created from 2006 to 2015. Patients with EBM who received high-dose-rate brachytherapy were included. Cough, dyspnea, chest pain, and hemoptysis were assessed and graded (0-4) at the time of initial consult and in followup. Symptom-free survival and re-expansion were assessed. ResultsThirty-five patients with EBM were identified. Most patients received three fractions of 700 cGy, and 17 patients had prior external beam radiotherapy. Median symptom-free and overall survival were 67 and 117 days. After brachytherapy, improvement in cough was documented in 75.0%, hemoptysis in 76.4%, dyspnea in 60.0% for a median of 3-6 months. Of the 22 patients who had subsequent chest imaging, re-expansion was documented in 32%. There were no significant toxicities reported. ConclusionsBrachytherapy appears effective in achieving durable symptom control of cough hemoptysis, and dyspnea in patients with EBM and should be considered routinely for palliation where available. Further studies are required to better characterize expected symptom improvement, lung re-expansion rates, and efficacy in comparison with other local treatments.

Triple-tandem high-dose-rate brachytherapy for early-stage medically inoperable endometrial cancer: Initial report on acute toxicity and dosimetric comparison to stereotactic body radiation therapy

PurposeStereotactic body radiotherapy (SBRT) may be appealing in medically inoperable endometrial cancer to avoid procedural risks. We performed a dosimetric comparison to triple-tandem, high-dose-rate (HDR) brachytherapy. Methods and MaterialsSix consecutive clinical stage I, grade 1–2, medically inoperable endometrial cancer patients were treated with triple-tandem HDR brachytherapy. We report patient factors and acute toxicity. Also, we performed dosimetric comparison to SBRT using both 3D conformal arc (3DArc) and volumetric-modulated arc therapy. D2cc values for normal tissues were calculated and compared to the HDR plans. ResultsMedian age was 57 years. Patient comorbidities included morbid obesity, congestive heart failure, diabetes, and pulmonary emboli. In three patients who received prior external beam radiation (EBRT), median EBRT and HDR doses were 46 Gy and 20 Gy, respectively. The median dose with HDR brachytherapy monotherapy was 35 Gy. Acute toxicities during EBRT included gastrointestinal (3/3 with grade 1–2) and genitourinary (3/3 with grade 1–2). Acute toxicities during HDR brachytherapy were gastrointestinal (2/6 total with grade 1–2) and genitourinary (2/6 total with grade 1). The mean D2cc/Gy of prescription dose for rectum, sigmoid, and bladder were 0.58, 0.40, and 0.47 respectively. Overall, doses to normal tissues were higher for SBRT plans as compared to HDR. Also, the R50 (ratio of the 50% prescription isodose volume to the PTV) was lowest with HDR brachytherapy. ConclusionsIn medically inoperable, clinical stage I endometrial cancer patients with multiple comorbidities, definitive triple-tandem, HDR brachytherapy results in mild acute toxicity. In addition, HDR brachytherapy achieves relatively lower doses to surrounding normal tissues as compared to SBRT.

PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure

Background:Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting.Methods:An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005–2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml−1)), start of systemic therapies or metastases.Results:Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64–72), 5.9 ng ml−1 (2.2–11.3) and 7 (6–9), respectively. Median follow-up was 64 months (49–84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml−1, 15/50 (30%) had a nadir ⩾0.5 ng ml−1 and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml−1, nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%).Conclusions:In our series of high-risk patients, in whom 30–50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.

Automation of Treatment Planning Goals Documentation in HDR Brachytherapy

Automation of Treatment Planning Goals Documentation in HDR Brachytherapy

Distal Vaginal Recurrences after Vaginal Brachytherapy

Distal Vaginal Recurrences after Vaginal Brachytherapy

Utility of prostate multiparametric MRI (mpMRI) for recurrent prostate cancer after radiation therapy and cryotherapy.

71 Background: We evaluated the accuracy of mpMRI for identifying locally recurrent prostate cancer after primary radiotherapy and cryotherapy. Methods: Between 2009-2015, 61 patients with evidence of rising PSA after external-beam radiotherapy (EBRT) (N = 33), brachytherapy (N = 6), and cryotherapy (N = 22) were evaluated for locally recurrent prostate cancer with mpMRI and prostate biopsy. Of these patients, 6 (10%) received androgen deprivation therapy (ADT) in combination with EBRT for a median of 24 months. Three of the cryotherapy patients received prior EBRT. Patients were identified from a prospective mpMRI database. All patients with a lesion of interest (LOI) underwent a ≥ 12-core, post-mpMRI cognitive fusion prostate biopsy. We excluded 16 patients with mpMRI who did not undergo prostate biopsy (5 positive, 11 negative). Results: Median age was 70 (IQR: 64-77). The median time from primary treatment to mpMRI was 5 years (IQR: 3-9) and the median PSA at mpMRI was 3.6 ng/mL (IQR: 2.1-5.5). Median prostate volume was 18.8 cc (IQR: 11.0-28.0 cc). mpMRI revealed lesions of interest (LOI) in 39 (64%) and 41 (67%) had biopsy-proven local recurrence. Of the 22 patients with negative mpMRI, 8 (36%) had a positive biopsy, with a median prostate volume of 19 cc, median maximum cancer length of 5 mm, median PSA of 2.5 and biopsy Gleason scores 3+3 (N = 1), 4+3 (N=2), 5+4 (N = 1), 5+5 (N = 1) and ungraded due to treatment effect (N = 3). Of the 39 patients with LOI on mpMRI, 33 (85%) had a positive biopsy. Table 1 summarizes the mpMRI and biopsy results. The sensitivity, specificity, PPV and NPV of mpMRI to predict cancer diagnosis at biopsy was 80.5%, 70.0%, 84.6% and 63.6%, respectively. On univariate analysis, gland size (p=0.367), PSA (p=0.872), biopsy Gleason score (p=0.892) and primary treatment modality (p=0.177) did not significantly predict discrepancy between mpMRI and biopsy findings. Conclusions: mpMRI reliably identifies prostate cancer recurrence after primary radiation therapy and cryoablation. [Table: see text]

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

F31 - External beam radiation therapy (EBRT) use and safety with radium-223 dichloride (Ra-223) in patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) from the ALSYMPCA trial

Background: In ALSYMPCA, Ra-223, a first-in-class &agr;-emitter, improved overall survival and delayed time to first symptomatic skeletal event vs placebo (pbo). This post hoc analysis evaluated safety and efficacy of Ra-223 plus EBRT. Methods: Pts had symptomatic (recent EBRT for bone pain or any regular analgesic use) CRPC with ≥ 2 bone and no visceral mets; best standard of care; and prior docetaxel (pD) or were unfit for or declined docetaxel (no pD). Pts were stratified by pD use (yes/no), baseline total alkaline phosphatase level (tALP; < 220 U/L or ≥ 220 U/L), and current bisphosphonate (bp) use (yes/no) and randomized 2:1 to 6 Ra-223 injections (50 kBq/kg IV q 4 wk) or pbo. EBRT for bone pain was permitted within 12 weeks prior to randomization and during study. Baseline pain by prior EBRT, time to first on-study EBRT use for bone pain, and adverse events (AEs) by concomitant EBRT (cEBRT) were analyzed. Results: Pts with no prior EBRT had less pain at baseline; a WHO pain score ≤ 1 (no opioid use) was present in 46% (355/724) of pts with no prior EBRT vs 36% (53/147) of pts with prior EBRT. Ra-223 vs pbo significantly reduced EBRT use in the overall population (HR = 0.67, P = 0.001) and in pts with ≤ 20 bone mets (HR = 0.49, P < 0.001), current bp use (HR = 0.47, P = 0.004), tALP < 220 U/L (HR = 0.66, P = 0.008), and no pD (HR = 0.65, P = 0.038). At 6 months, the percentage of Ra-223 pts requiring EBRT was similar for prior and no prior EBRT subgroups (24% vs 20%), increasing at 12 months (38% vs 29%). cEBRT did not affect Ra-223 safety, and myelosuppression was low (Table). Conclusions: cEBRT did not adversely affect Ra-223 hematologic safety. Ra-223 significantly reduced risk of EBRT use. In Ra-223 pts, prior EBRT did not appear to affect later EBRT use. Clinical trial information: NCT00699751Table: F31cEBRTcEBRTNo cEBRTNo cEBRTPatients with AEs, n (%)Ra-223n = 227Pbon = 140Ra-223n = 373Pbon = 161HematologicAnemia77 (34)51 (36)110 (30)41 (26)Neutropenia14 (6)1 (1)16 (4)2 (1)Thrombocytopenia27 (12)8 (6)42 (11)9 (6)NonhematologicDiarrhea71 (31)26 (19)80 (21)19 (12)Nausea98 (43)61 (44)115 (31)43 (27)Vomiting56 (25)26 (19)55 (15)15 (9)Constipation54 (24)35 (25)54 (15)29 (18) Open table in a new tab

Stereotactic body radiotherapy for head and neck cancer: an addition to the armamentarium against head and neck cancer.

In the recent years, stereotactic body radiation therapy (SBRT) has emerged as a potential therapy for head and neck malignancies. Although early results appear to be promising, serious acute and late effects have been observed, mainly in patients who have had prior external beam radiotherapy. This review will discuss the radiobiology of SBRT, clinical rationale and outcomes for SBRT in head and neck cancers and focus on the benefits and potential limitations in both de novo and re-irradiation settings.