5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Refining complex re-irradiation dosimetry through feasibility benchmarking and analysis for informed treatment planning.

PURPOSE/OBJECTIVES: The purpose of this study is to dually evaluate the effectiveness of PlanIQ in predicting the viability and outcome of dosimetric planning in cases of complex re-irradiation as well as generating an equivalent plan through Pinnacle integration. The study also postulates that a possible strength of PlanIQ lies in mitigating pre-optimization uncertainties tied directly to dose overlap regions where re-irradiation is necessary. METHODS: A retrospective patient selection (n = 20) included a diverse range of re-irradiation cases to be planned using Pinnacle auto-planning with PlanIQ integration. A consistent planning template was developed and applied across all cases. Direct plan comparisons of manual plans against feasibility-produced plans were performed by physician(s) with dosimetry recording relevant proximal OAR and planning timeline data. RESULTS AND DISCUSSION: All re-irradiation cases were successfully predicted to be achievable per PlanIQ analyses with three cases (3/20) necessitating 95% target coverage conditions, previously exhibited in the manually planned counterparts, and determined acceptable under institutional standards. At the same time, PlanIQ consistently produced plans of equal or greater quality to the previously manually planned re-irradiation across all (20/20) trials (P = 0.05). Proximal OAR exhibited similar to slightly improved maximum point doses from feasibility-based planning with the largest advantages gained found within the subset of cranial and spine overlap cases, where improvements upward of 10.9% were observed. Mean doses to proximal tissues were found to be a statistically significant (P < 0.05) 5.0% improvement across the entire study. Documented planning times were markedly less than or equal to the time contributed to manual planning across all cases. CONCLUSION: Initial findings indicate that PlanIQ effectively provides the user clear feasibility feedback capable of facilitating decision-making on whether re-irradiation dose objectives and prescription dose coverage are possible at the onset of treatment planning thus eliminating possible trial and error associated with some manual planning. Introducing model-based prediction tools into planning of complex re-irradiation cases yielded positive outcomes on the final treatment plans.

Comparison of multiparametric MRI-based and transrectal ultrasound-based preplans with intraoperative ultrasound-based planning for low dose rate interstitial prostate seed implantation.

PURPOSE: Transrectal ultrasound images are routinely acquired for low dose rate (LDR) prostate brachytherapy dosimetric preplanning (pTRUS), although diagnostic multiparametric magnetic resonance imaging (mpMRI) may serve this purpose as well. We compared the predictive abilities of TRUS vs MRI relative to intraoperative TRUS (iTRUS) to assess the role of mpMRI in brachytherapy preplanning. MATERIALS AND METHODS: Retrospective analysis was performed on 32 patients who underwent iTRUS-guided prostate LDR brachytherapy as either mono- or combination therapy. 56.3% had pTRUS-only volume studies and 43.7% had both 3T-mpMRI and pTRUS preplanning. MRI was used for preplanning and its image fusion with iTRUS was also used for intraoperative guidance of seed placement. Differences in gland volume, seed number, and activity and procedure time were examined, as well as the identification of lesions suspicious for tumor foci. Pearson correlation coefficient and Fisher's Z test were used to estimate associations between continuous measures. RESULTS: There was good correlation of planning volumes between iTRUS and either pTRUS or MRI (r = 0.89, r = 0.77), not impacted by the addition of hormonal therapy (P = 0.65, P = 0.33). Both consistently predicted intraoperative seed number (r = 0.87, r = 0.86). MRI/TRUS fusion did not significantly increase surgical or anesthesia time (P = 0.10, P = 0.46). mpMRI revealed suspicious focal lesions in 11 of 14 cases not visible on pTRUS, that when correlated with histopathology, were incorporated into the plan. CONCLUSIONS: Relative to pTRUS, MRI yielded reliable preplanning measures, supporting the role of MRI-only LDR treatment planning. mpMRI carries numerous diagnostic, staging and preplanning advantages that facilitate better patient selection and delivery of novel dose escalation and targeted therapy, with no additional surgical or anesthesia time. Prospective studies assessing its impact on treatment planning and delivery can serve to establish mpMRI as the standard of care in LDR prostate brachytherapy planning.

Advances in Radiotherapy for Prostate Cancer Treatment.

Major categories of radiotherapy (RT) for prostate cancer (CaP) treatment are: (1) external beam RT (EBRT), and (2) brachytherapy (BT). EBRT are performed using different techniques like three-dimensional conformal RT (3D-CRT), intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT), stereotactic radiosurgery (SRS) and intensity modulated proton therapy (IMPT), etc., using a variety of radiation delivery machines, such as a linear accelerator (Linac), Cyberknife robotic system, Gamma knife, Tomotherapy and proton beam machine. The primary advantage of proton beam therapy is sparing of normal tissues and organ at risks (OARs) with comparable coverage of the tumor volume. MR-Linac is the latest addition in the image-guided RT. Robot-assisted brachytherapy is one of the latest technological innovations in the field. With the advancement of technology, radiation therapy for prostate cancer can be improved using high quality multimodal imaging, robot-assistance for brachytherapy as well as EBRT. This chapter presents the advances in radiation therapy for the treatment of prostate cancer.

Reduction of seed motion using a bio-absorbable polymer coating during permanent prostate brachytherapy using a mick applicator technique.

PURPOSE: The addition of a braided bio-absorbable vicryl coating to the surface of radioactive seeds used for low dose rate (LDR) prostate brachytherapy is intended to reduce the incidence of seed movement and migration. Here, we present a single-institution study of the frequency and severity of seed slippage (initial seed movement) of coated seeds in comparison with uncoated seeds. METHODS: Forty-seven patients received permanent prostate brachytherapy, with either coated (n = 26) or uncoated (n = 21) seeds. AgX100 125 I seeds, coated or uncoated, and uncoated Model 200 103 Pd seeds were used. During the ultrasound-guided implantation procedure, each implanted seed was categorized as having remained in the implanted position after being placed, having moved slightly, or having left the ultrasound field of view. RESULTS: 3.1% of the coated seeds (AgX100 seeds, n = 70) and 6.9% of the uncoated seeds (AgX100 and Model 200 seeds, n = 128) were observed to have moved at least 2 mm from their initial implant positions, respectively. The difference in incidence of this movement was 54.4% (P = 0.0026). Coated AgX100 seeds demonstrated a 66.7% lower rate of movement of at least 2 mm than that for uncoated AgX100 seeds (P = 0.038), and a 49.0% lower rate than that for Model 200 seeds (P = 0.021). While no significant differences were noted in prescription dose coverage of the prostate or the studied dosimetric parameters for the organs at risk between the coated and uncoated seeds (P > 0.05) in the CT-based Day-0 postoperative plans, the limited sample size and differences in energies between the 125 I and 103 Pd seeds make further analysis of postoperative dosimetric coverage difficult without additional data directly comparing the coated and uncoated 125 I seeds. CONCLUSION: When the vicryl coating is used, seeds have a significantly lower propensity to slip from their initial implant locations. This may help maintain dosimetric integrity, warranting further study of postoperative dosimetry.

Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma.

AIM: To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. MATERIALS & METHODS: Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. RESULTS: All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. CONCLUSION: Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.

Real-time in vivo dosimetry for SBRT prostate treatment using plastic scintillating dosimetry embedded in a rectal balloon: a case study.

A novel FDA approved in vivo dosimetry device system using plastic scintillating detectors placed in an endorectal balloon to provide real-time in vivo dosimetry for prostatic rectal interface was tested for use with stereotactic body radiotherapy (SBRT). The system was used for the first time ever to measure dose during linear accelerator based SBRT. A single patient was treated with a total dose of 36.25 Gy given in 5 fractions. Delivered dose was measured for each treatment with the detectors placed against the anterior rectal wall near the prostate rectal interface. Measured doses showed varying degrees of agreement with computed/ planned doses, with average combined dose found to be within 6% of the expected dose. The variance between measurements is most likely due to uncertainty of the detector location, as well as variation in the placement of a new balloon prior to each fraction. Distance to agreement for the detectors was generally found to be within a few millimeters, which also suggested that the differences in measured and calculated doses were due to positional uncertainty of the detectors during the SBRT, which had sharp dose falloff near the penumbra along the rectal wall. Overall, the use of a real time in vivo dosimeter provided a level of safety and improved confidence in treatment delivery. We are evaluating the device further in an IRB-approved prospective partial prostate SBRT trial, and believe further clinical investigations are warranted.

Chest wall and rib irradiation and toxicities of early-stage lung cancer patients treated with CyberKnife stereotactic body radiotherapy.

AIM: The aim of the study is to evaluate the chest wall and rib toxicities in primary lung cancer patients treated with CyberKnife-based stereotactic body radiotherapy. MATERIALS & METHODS: In this study, data were collected from the 118 patients, of which 25 patients who had longer follow-up (mean: 21.9 months) were considered. Studied parameters were maximum point dose, doses to 1-100 cm(3) of chest wall and 1-10 cm(3) of ribs. RESULTS: Three patients developed chest wall pain (grade I). 25 studied patients, on average, received 27.7 Gy to 30 cm(3) of chest wall and 50.4 Gy to 1 cm(3) of rib. Nine patients had more than 30 Gy dose to 30 cm(3) of chest wall. No rib bone fracture was found. CONCLUSION: No correlations of chest wall pain and volume of irradiation were found.

Stereotactic body radiotherapy: an effective local treatment modality for hepatocellular carcinoma.

Although liver-directed therapies such as surgery or ablation can cure hepatocellular carcinoma, few patients are eligible due to advanced disease or medical comorbidities. In advanced disease, systemic therapies have yielded only incremental survival benefits. Historically, radiotherapy for liver cancer was dismissed due to concerns over unacceptable toxicities from even moderate doses. Although implementation requires more resources than standard radiotherapy, stereotactic body radiotherapy can deliver reproducible, highly conformal ablative radiotherapy to tumors while minimizing doses to nearby critical structures. Trials of stereotactic body radiotherapy for hepatocellular carcinoma have demonstrated promising local control and survival results with low levels of toxicity in Child-Pugh class A patients. We review the published literature and make recommendations for the future of this emerging modality.

Emerging applications of stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) has been used extensively in patients with lung, liver and spinal tumors, and the treatment outcomes are very favorable. For certain conditions such as medically inoperable stage I non-small-cell lung cancer, liver and lung oligometastases, primary liver cancer and spinal metastases, SBRT is regarded as one of the standard therapies. In the recent years, the use of SBRT has been extended to other disease conditions and sites such as recurrent head and neck cancer, renal cell carcinoma, prostate cancer, adrenal metastasis, pancreatic cancer, gynecological malignancies, spinal cord compression, breast cancer, and stage II-III non-small-cell lung cancer. Preliminary data in the literature show promising results but the follow-up intervals are short for most studies. This paper will provide an overview of these emerging applications.