While the standard of care for anal cancer consists of concurrent chemoradiation, patients with advanced T stages often succumb to local failures. Salvage treatment consists of an abdominoperineal resection (APR). While this is a good surgery to treat the local recurrence, there may be a risk of obtaining a positive margin due to the advanced nature and location of the recurrence. Addressing these high-risk positive margin sites with adjuvant brachytherapy after surgical resection is a good option to deliver a high dose of radiation to the R1 resection site while sparing the adjacent critical organs at risk. Herein, we present a case report of two patients with persistent or recurrent anal cancer who were treated with an APR with placement of a custom Cesium-131 brachytherapy mesh implant.

Purpose/Objective(s) Cachexia is a metabolic state leading to weight loss from both muscle volume and adipose tissue loss. Cancer cachexia is believed to impact over 50% of cancer patients. Several studies have shown cachexia to be an independent prognostic indicator of worse outcomes. Endometrial cancer represents a unique patient population in which cachexia may be under-diagnosed secondary to obesity. Our aim was to assess the impact of cachexia on progression-free survival (PFS) in patients with locally advanced endometrial cancer enrolled on recent cooperative group trials. Materials/Methods Eligible patients were selected from those enrolled on NRG/GOG-258 and NRG/RTOG 1203. All patients underwent a hysterectomy for stages IB, grade 3 to IVA (FIGO 2009) disease. The study required patient images from the radiation (RT) planning CT scans. Several cachexia indices (skeletal muscle area [SMA], skeletal muscle index [SMI]) were assessed by measuring and averaging the volume on two consecutive axillary images at the mid-level of the L3 vertebral body. The SMA was calculated by adding and averaging the volumes of both the paraspinal muscles [PS SMA] and abdominal muscles [ABD SMA] at L3. The L3 SMI, a well-established cancer cachexia index, was calculated. Cachexia cutoffs were determined based on volume measurements of all eligible patients. PFS was estimated using the Kaplan-Meier method. Cox proportional hazards models, adjusted for treatment arm, were used to identify cachexia indices associated with PFS. Results In total, 422 patients had baseline characteristics available for evaluation: 119 (28%) patients in the RTOG-1203 control 3D RT arm, 110 (26%) in the IMRT arm, and 193 (46%) in the GOG-258 chemoradiation arm. The median age of the combined cohort was 62 (IQR: [55-68]). The median BMI was 32 (IQR: [26, 38]), with 20% and 59% categorized as overweight and obese, respectively. 228 (54%) patients had imaging and BMI data available to calculate cachexia indices. Cachexia based on L3 SMA (<30 vs. ≥30) was associated with worse PFS (HR = 1.71, P = 0.014), whereas L3 SMI (<12000 vs ≥12000) was not associated with PFS (HR = 1.39; P = 0.13). When evaluating individual muscle groups, cachexia in the paraspinal SMA alone was also significantly associated with worse PFS (HR = 1.74, p = 0.013), but not in the abdominal SMA alone (P = 0.181). Conclusion Endometrial cancer represents a unique cancer population, and as such, cancer cachexia is not well studied. In this secondary analysis of patients with locally advanced endometrial cancer from RTOG 1203 and GOG 258, L3 SMI cachexia was not associated with worse outcomes. However, other cachexia indices in this patient population (L3 and PSA SMA) were found to be associated with higher recurrences and significantly worse PFS. This study demonstrates that traditional measures of cachexia may not extrapolate to endometrial cancer and other indices may be required.

PURPOSE Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Objectives The pelvis is a common site of recurrence for patients with endometrial cancers. A randomized trial was conducted to compare progression-free survival in patients treated with radiation therapy alone as compared to radiation therapy with concurrent cisplatin-based chemotherapy. Methods 165 Patients were accrued between February 2009 and August 2020. Women with recurrent endometrial carcinoma limited to the pelvis were eligible. The median time for follow up for vital status was 60 months. Results Most patients had grade 1 or 2 endometroid endometrial cancer (81%) and most recurrences were vaginal (86%). Radiation therapy was delivered to the pelvis with 3D or IMRT techniques followed by HDR or LDR interstitial or intracavitary brachytherapy. Chemotherapy was delivered with weekly cisplatin. Grade 4 or higher acute adverse event were reported in 8 participants in the chemotherapy and radiation arm as compared to 1 treated with radiation only. 68% of patients treated with radiation therapy were alive and progression-free as compared to 59.8% of those that received chemotherapy and radiation. Overall, patients treated with weekly cisplatin had a lower rate of PFS as compared to patients treated with radiation alone (stratified HR=1.40, 95% CI: 0.82–2.39, p=0.8919). Conclusions Results of this randomized trial suggest that the addition of chemotherapy does not improve, and may worsen, outcomes for patients treated with definitive radiation therapy for recurrent endometrial cancer. Those with low grade and vaginal apex recurrences may be best treated with radiation therapy alone.

Introduction. Chemotherapy plus radiation (Cis-RT + CP) did not demonstrate superiority in prolonging relapse-free survival compared to chemotherapy alone in patients with stage III or IVA endometrial carcinoma. The impact of treatment on quality of life (QOL), neurotoxicity (NTX) and psychometric properties of the gastrointestinal (GI) symptoms subscale during treatment and up to 1 year are described herein. Methods. QOL assessments were scheduled at baseline, 6 weeks (post completion of RT (Cis-RT + CP) or prior to cycle 3 (CP)), then 18 weeks (end of treatment) and 70 weeks (1 year after the end of treatment) after starting treatment. QOL instruments included the FACT-En TOI, FACT/GOG-neurotoxicity (Ntx) subscale (short), and the gastrointestinal (GI) symptoms subscale. Results. At the end of treatment, patients receiving Cis-RT + CP reported a statistically significant decreased QOL when compared to CP. The decline in QOL was reflected in physical well-being, functional well-being, and endometrial cancer specific concerns, but the minimally important differences (MID) were not considered clinically meaningful. Patients in both groups reported increased chemotherapy-induced Ntx symptoms with the CP group having worse scores and reaching peak symptoms at the time of chemotherapy completion. Patients on Cis-RT + CP reported statistically significantly worse GI symptoms after radiation therapy compared to patients on CP, this occurred across assessment intervals, though the MID was not meaningful. Psychometric evaluations indicated that the GI symptom scale is reliable, valid, and responsive to change. Conclusions. PROs indicate that the chemoradiotherapy group experienced worse HRQoL and GI toxicity compared to patients randomized to chemotherapy alone for locally advanced endometrial cancer though based on the MID, these were not clinically meaningful differences. The GI symptom subscale was a reliable and valid scale that has value for future trials. Trial registration: NCT00942357 (c) 2021 Elsevier Inc. All rights reserved.

Health inequities and decreasing median American lifespan, potentiated by the worldwide COVID 19 crisis, have taken centre stage in the public consciousness. Specifically, for this discourse, rural radiation oncology challenges external to the pandemic and unique to the rural American radiation oncology care delivery result from a confluence of the following: a) increased incidence of cancer in the United States; b) recent legislative emphasis on rural healthcare equity initiatives; c) pandemic-associated delays in cancer screening, diagnosis, and treatment with resultant presentation of advanced oncologic stages; d) social spotlight on healthcare equity and inclusion for disenfranchised populations. We will attempt to delineate these issues and propose widely applicable common-sense solutions. We will review what has transpired at the University of Kentucky over the last two decades, specifically at radiation oncology centre in Morehead, a clinic in eastern Kentucky in the Appalachian foothills. While much more work remains ahead, this clinic has successfully applied many of the initiatives discussed. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Abstract Purpose Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m‐bm) when using single‐isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT‐VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. Material and Methods Nine complex patients with 61 total tumors (2‐16 tumors/patient) were planned using SIMT‐VMAT with geometry similar to HyperArc with a 10MV‐FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m‐bm via SIMT‐VMAT. Results Patient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. Conclusions Radiosurgery of m‐bm using SIMT‐VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation‐induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m‐bm using a SIMT‐VMAT plan.

Single-isocenter volumetric modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) techniques to treat multiple brain metastases simultaneously can significantly improve treatment delivery efficiency, patient compliance, and clinic workflow. However, due to large number of brain metastases sharing the same MLC pair causing island blocking, there is higher low- and intermediate-dose spillage to the normal brain and higher dose to organs-at-risk (OAR). To minimize this problem and improve plan quality, this study proposes a dual-isocenter planning strategy that groups lesions based on hemisphere location (left vs right sided) in the brain parenchyma, providing less island blocking reducing the MLC travel distance. This technique offers simplified planning while also increasing patient comfort and compliance by allowing for large number of brain metastases to be treated in 2 groups. Seven complex patients with 5 to 16 metastases (64 total) were planned with a single-isocenter VMAT-SRS technique using a 10MV-FFF beam with a prescription of 20 Gy to each lesion. The isocenter was placed at the approximate geometric center of the targets. Each patient was replanned using the dual-isocenter approach, generating 2 plans and placing each isocenter at the approximate geometric center of the combined targets of each side with corresponding non-coplanar partial arcs. Compared to single-isocenter VMAT, dual-isocenter VMAT plans provided similar target coverage and dose conformity with less spread of intermediate dose to normal brain with reduction of dose to OAR. Reduction in total monitor units and beam on time was observed, but due to the second isocenter setup and verification, overall treatment time was increased. Dual-isocenter VMAT-SRS planning for multiple brain metastases is a simplified approach that provides superior treatment options for patient compliance who may not tolerate longer traditional treatment times as with individual isocenters to each target. This planning technique significantly reduces the amount of low- and intermediate-dose spillage, further sparing OAR and normal brain, potentially improving target accuracy though localization of left vs right-sided tumors for each isocenter set up.

Uterine cervix cancer (UCCx) is clinically and socioeconomically diverse among women in the United States (US), which obscures the discovery of effective radiochemotherapy approaches for this disease. UCCx afflicts 7.5 per 100,000 American women nationally but 11.7 per 100,000 women in Appalachian Kentucky (AppKY), when age-adjusted to the 2000 US standard population. Epidemiological chart review was performed on 212 women with UCCx treated at the University of Kentucky (UKY) between January 2001 and July 2021. Demographics, tumor characteristics, and relative radiochemotherapy dose and schedule intensity were compared among AppKY and non-AppKY cohorts as well as Surveillance, Epidemiology, and End Results (SEER) data. One hundred thirty-eight (65%) of 212 women seeking radiochemotherapy treatment for UCCx resided in AppKY. Most (80%) sought external-beam radiochemotherapy close to their AppKY residence. Brachytherapy was then most frequently (96%) conducted at UKY. Cancer stage at diagnosis was significantly more advanced in AppKY residents. Women residing in AppKY had a median 10-week radiochemotherapy course, longer than an 8-week guideline. Estimated survival in women residing in AppKY was 8% lower than US national averages. In summary, this study identified an increased percentage of advanced-stage UCCx cancer at diagnosis arising in AppKY residents, with a confounding population-specific delay in radiochemotherapy schedule intensity lowering survival.

AbstractPurposeTo develop a knowledge‐based planning (KBP) routine for stereotactic body radiotherapy (SBRT) of peripherally located early‐stage non‐small‐cell lung cancer (NSCLC) tumors via dynamic conformal arc (DCA)‐based volumetric modulated arc therapy (VMAT) using the commercially available RapidPlanTM software. This proposed technique potentially improves plan quality, reduces complexity, and minimizes interplay effect and small‐field dosimetry errors associated with treatment delivery.MethodsKBP model was developed and validated using 70 clinically treated high quality non‐coplanar VMAT lung SBRT plans for training and 20 independent plans for validation. All patients were treated with 54 Gy in three treatments. Additionally, a novel k‐DCA planning routine was deployed to create plans incorporating historical three‐dimensional‐conformal SBRT planning practices via DCA‐based approach prior to VMAT optimization in an automated planning engine. Conventional KBPs and k‐DCA plans were compared with clinically treated plans per RTOG‐0618 requirements for target conformity, tumor dose heterogeneity, intermediate dose fall‐off and organs‐at‐risk (OAR) sparing. Treatment planning time, treatment delivery efficiency, and accuracy were recorded.ResultsKBPs and k‐DCA plans were similar or better than clinical plans. Average planning target volume for validation was 22.4 ± 14.1 cc (7.1–62.3 cc). KBPs and k‐DCA plans provided similar conformity to clinical plans with average absolute differences of 0.01 and 0.01, respectively. Maximal doses to OAR were lowered in both KBPs and k‐DCA plans. KBPs increased monitor units (MU) on average 1316 (P < 0.001) while k‐DCA reduced total MU on average by 1114 (P < 0.001). This routine can create k‐DCA plan in less than 30 min. Independent Monte Carlo calculation demonstrated that k‐DCA plans showed better agreement with planned dose distribution.ConclusionA k‐DCA planning routine was developed in concurrence with a knowledge‐based approach for the treatment of peripherally located lung tumors. This method minimizes plan complexity associated with model‐based KBP techniques and improve plan quality and treatment planning efficiency.

The 3D MLC-based forward planned GRID therapy enhanced target dose for bulky masses including deep-seated large tumors while protecting skin and adjacent critical organs. This same day MLC-GRID treatment provides safe, effective, and convenient treatment by eliminating the risk to therapists and patient of heavy gantry-mounted physical GRID-block. This rapid 3D MLC-GRID planning and treatment can be easily adopted by any radiation clinics on the same day eliminating the need of longer plan optimization and patient-specific quality assurance. MLC-GRID provides all the dosimetry information in the planning system and potentially allow escalating dose to the bulky masses. It may allow for debulking of unresectable large tumors-opening an avenue for a neoadjuvant treatment option. Clinical follow up of these patients is ongoing.

L. Downes: None. D. Pokhrel: None. L. Critchfield: None. M.E. Bernard: None. M.E. Randall: None. R.C. McGarry: None.

Until last year I thought that cancel culture on social media was something that only affected celebrities and politicians. Then I became the target of a campaign that was personally insulting and professionally alarming. The issue is how some members of our profession react to disagreement about accepted views. My offense was questioning the concept that we are training too many radiation oncologists. But the workforce controversy is not the point of this essay. The point is that challenging accepted concepts has been the driving force for the most positive advances in our field, and the uncivil, anonymous, and often inaccurate criticism that social media now encourages threatens progress in the future.

I want to share the excitement and amazement I felt when I learned about the role of radiation therapy in the first human heart transplant. For me, this story is a reminder to keep our eyes open to the world around us as we go about our daily lives, because unexpected gems of insight, interest, and wonder are waiting to be discovered if we are simply curious. When I learned that radiation therapy played a role in one of medicine's most dramatic milestones, it was such a thrill to me as a radiation oncologist. My curiosity was greatly rewarded, and it's a great story to tell.

Synchronous treatment of two lung lesions using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can decrease treatment time and reduce the impact of intrafraction motion. However, alignment of both lesions on a single cone beam CT (CBCT) can prove difficult and may lead to setup errors and unacceptable target coverage loss. A Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST) method was created to minimize setup uncertainties and provide treatment delivery flexibility. RESIST utilizes a single-isocenter placed at patient's midline and allows both lesions to be planned separately but treated in the same session. Herein is described a process of automation of this novel RESIST method. Automation of RESIST significantly reduced treatment planning time while maintaining the benefits of RESIST. To demonstrate feasibility, ten patients with two lung lesions previously treated with a single-isocenter clinical VMAT plan were replanned manually with RESIST (m-RESIST) and with automated RESIST (a-RESIST). a-RESIST method automatically sets isocenter, creates beam geometry, chooses appropriate dose calculation algorithms, and performs VMAT optimization using an in-house trained knowledge-based planning model for lung SBRT. Both m-RESIST and a-RESIST showed lower dose to normal tissues compared to manually planned clinical VMAT although a-RESIST provided slightly inferior, but still clinically acceptable, dose conformity and gradient indices. However, a-RESIST significantly reduced the treatment planning time to less than 20 min and provided a higher dose to the lung tumors. The a-RESIST method provides guidance for inexperienced planners by standardizing beam geometry and plan optimization using DVH estimates. It produces clinically acceptable two lesions VMAT lung SBRT plans efficiently. We have further validated a-RESIST on phantom measurement and independent pretreatment dose verification of another four selected 2-lesions lung SBRT patients and implemented clinically. Further development of a-RESIST for more than two lung lesions and refining this approach for extracranial oligometastastic abdominal/pelvic SBRT, including development of automated simulated collision detection algorithm, merits future investigation.

AbstractPurposeTo demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge‐based planning (KBP) model to support offline adaptive radiotherapy.Materials/methodsTwenty previously treated non‐coplanar volumetric‐modulated arc therapy (VMAT) lung SBRT plans (c‐Truebeam) on SBRT‐dedicated C‐arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c‐Truebeam plans were re‐optimized for Halcyon manually (m‐Halcyon) and with KBP model (k‐Halcyon). Both m‐Halcyon and k‐Halcyon plans were normalized for identical or better target coverage than clinical c‐Truebeam plans and compared for target conformity, dose heterogeneity, dose fall‐off, and dose tolerances to the organs‐at‐risk (OAR). Treatment delivery parameters and planning times were evaluated.Resultsk‐Halcyon plans were dosimetrically similar or better than m‐Halcyon and c‐Truebeam plans. k‐Halcyon and m‐Halcyon plan comparisons are presented with respect to c‐Truebeam. Differences in conformity index were statistically insignificant in k‐Halcyon and on average 0.02 higher (p = 0.04) in m‐Halcyon plans. Gradient index was on average 0.43 (p = 0.006) lower and 0.27 (p = 0.02) higher for k‐Halcyon and m‐Halcyon, respectively. Maximal dose 2 cm away in any direction from target was statistically insignificant. k‐Halcyon increased maximal target dose on average by 2.9 Gy (p < 0.001). Mean lung dose was on average reduced by 0.10 Gy (p = 0.004) in k‐Halcyon and increased by 0.14 Gy (p < 0.001) in m‐Halcyon plans. k‐Halcyon plans lowered bronchial tree dose on average by 1.2 Gy. Beam‐on‐time (BOT) was increased by 2.85 and 1.67 min, on average for k‐Halcyon and m‐Halcyon, respectively. k‐Halcyon plans were generated in under 30 min compared to estimated dedicated 180 ± 30 min for m‐Halcyon or c‐Truebeam plan.Conclusionk‐Halcyon plans were generated in under 30 min with excellent plan quality. This adaptable KBP model supports high‐volume clinics in the expansion or transfer of lung SBRT patients to Halcyon.

Cone-beam computed tomography (CT)-guided volumetric-modulated arc therapy (VMAT) plans for stereotactic body radiotherapy (SBRT) treatment of synchronous multiple lung lesions with a flattening filter-free (FFF) beam is a safe and highly effective treatment option for oligometastases lung cancer patients. Fourteen patients with metastatic non-small-cell lung cancer (NSCLC) lesions (two to five) received a single-isocenter VMAT SBRT treatment in our clinic. Four-dimensional (4D) CT-based treatment plans were generated using advanced AcurosXB-based dose calculation algorithm using heterogeneity corrections with a single isocenter placed between/among the lesions. Compared to 10X-FFF and traditional flattened 6X (6X-FF) beams, 6X-FFF beam produced highly conformal radiosurgical dose distribution to each target volume, reduced dose to adjacent organs at risk (OAR), and significantly reduced the lung SBRT fraction duration to < 3.5 min/fraction for 54/50 Gy treatments in 3/5 fractions - significantly improving patient convenience and clinic workflow. Early follow-up CT imaging (mean, 9 months) results show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow up in a larger patient cohort is ongoing to further validate the outcomes of this treatment approach.

To present a novel and clinically useful 3D MLC-based forward planning technique for GRID therapy that provides fast, safe, and effective treatment delivery of larger ablative doses to deep-seated bulky tumors. Seven patients (3 head and neck, 1 chest, 1 breast, 1 para-spinal, 1 pelvis) with 7.0 to 12.0 cm diameter tumor sizes were treated using our novel MLC-based 3D-GRID therapy in our clinic. Standard Millenium120 MLC leaves were fitted to gross tumor volume (GTV) to generate 1 cm diameter holes and 2 cm center-to-center distance (at isocenter) mimicking traditional GRID-block pattern using an in-house algorithm. For a single-dose of 15 Gy, 3D MLC-based GRID plans were generated using 6-coplanar gantry positions at 60o spacing (210 o to 150 o) with 90o collimator rotation for a differentially-weighted 6–18MV beams. This MLC fitting algorithm in treatment planning system generates brachytherapy-like dose tunneling distributions without post-processing GTV-contour. Advanced Acuros-based dose was calculated. Dosimetric parameters evaluated include: GTVD50%, GTVD10% (hottest 10% of the GTV), GTV dose heterogeneities (peak-to-valley dose ratio, PVDR), skin dose, dose to immediately adjacent critical structures, and maximal dose 2 cm away from the GTV (D2cm). Additionally, planning time and delivery efficiency was recorded. All 3D-MLC GRID plans exhibited excellent target dose with mean GTVD50%, GTVD10% of 15 Gy being 7.5 ± 0.4 Gy (range: 7.4–8.3 Gy) and 12.4 ± 0.4 Gy (range: 11.2–12.9 Gy) or higher, respectively. Average PVDR and D2cm was 2.9 ± 0.5 (range: 2.5–3.8) and 64 ± 11% (range: 53–78%), respectively. Maximal and dose to 5 cc of skin were 10.6 ± 3.6 Gy (range: 5.5–13.1 Gy) and 6.5 ± 3.2 Gy (range: 2.6–10.5 Gy), on average, respectively. Immediately adjacent critical organs were spared: spinal cord (< 5.2 Gy), heart (< 5.7 Gy), femoral head (< 6.7 Gy) and small bowel (< 4.5 Gy). Average total monitor units and beam-on time was 1975 ± 93 and 3.3 ± 0.2 min, respectively. Overall treatment planning time was about an hour. This novel and clinically useful 3D MLC-based forward planning approach for GRID-therapy resulted in enhanced target dose for deep-seated bulky tumors, low skin toxicity and low doses to adjacent critical organs. This simple and fast MLC-based GRID therapy can be easily adopted by any radiotherapy clinic. It provides detailed dosimetry information and a safe and effective treatment option by eliminating physically heavy traditional single-field GRID-block and could provide same day treatment (by eliminating days of IMRT or Tomotherapy plan optimization and patient-specific quality assurance time) for debunking unresectable large tumors. It also allows for a greater chance for ablative doses for large tumors to provide optimal palliation and optimize local control with immunotherapy. Clinical follow up of these patients is underway and prospective clinical trial with escalated tumor-dose to bulky tumors is highly anticipated.