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Purpose: To evaluate the dosimetric impact on spatially fractionated radiation therapy (SFRT) plan quality due to intrafraction patient motion via multi‐field MLC‐based method for treating large and bulky (≥8 cm) unresectable tumors. Methods: For large tumors, a cone beam CT‐guided 3D conformal MLC‐based SFRT method was utilized with 15 Gy prescription. An MLC GTV‐fitting algorithm provided 1 cm diameter apertures with a 2 cm center‐to‐center distance at the isocenter. This generated a highly heterogeneous sieve‐like dose distribution within an hour, enabling same‐day SFRT treatment. Fifteen previously treated SFRT patients were analyzed (5 head & neck [H&N], 5 chest and lungs, and 5 abdominal and pelvis masses). For each plan, intrafraction motion errors were simulated by incrementally shifting original isocenters of each field in different x‐, y‐, and z‐directions from 1 to 5 mm. The dosimetric metrics analyzed were: peak‐to‐valley‐dose‐ratio (PVDR), percentage of GTV receiving 7.5 Gy, GTV mean dose, and maximum dose to organs‐at‐risk (OARs). Results: For ±1, ±2, ±3, ±4, and ±5 mm isocenter shifts: PVDR dropped by 3.9%, 3.8%, 4.0%, 4.1%, and 5.5% on average respectively. The GTV(V7.5) remained within 0.2%, and the GTV mean dose remained within 3.3% on average, compared to the original plans. The average PVDR drop for 5 mm shifts was 4.2% for H&N cases, 10% for chest and lung, and 2.2% for abdominal and pelvis cases. OAR doses also increased. The maximum dose to the spinal cord increased by up to 17 cGy in H&N plans, mean lung dose (MLD) changed was small for chest/lung, but the bowel dose varied up to 100 cGy for abdominal and pelvis cases. Conclusion: Due to tumor size, location, and characteristics of MLC‐based SFRT, isocenter shifts of up to ±5 mm in different directions had moderate effects on PVDR for H&N and pelvic tumors and a larger effect on chest tumors. The dosimetric impact on OAR doses depended on the treatment site. Site‐specific patient masks, Vac‐Lok bags, and proper immobilization devices similar to SBRT/SRT setups should be used to minimize these effects. [ABSTRACT FROM AUTHOR]

Objectives: Locally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. Methods: Patients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results: 19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. Conclusions: Lattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

Purpose: To compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy. Materials and Methods: PBS and volumetric modulated arc therapy (VMAT) GRID plans were retrospectively generated for 5 patients with bulky tumors. GRID targets were arranged along the long axis of the gross tumor, spaced 2 and 3 cm apart, and treated with a prescription of 18 Gy. PBS plans used 2- to 3-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak VPDR(D90/D10), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. The peak-to-valley dose ratio (PVDR), VPDR(D90/D10), and organ-at-risk doses were prospectively assessed in 2 patients undergoing PBS-GRID with pretreatment quality assurance computed tomography (QACT) scans. Results: PBS and VMAT GRID plans were generated for 5 patients with bulky tumors. Gross tumor volume values ranged from 826 to 1468 cm3. Peak-to-edge ratio for PBS was higher than for VMAT for both spacing scenarios (2-cm spacing, P = .02; 3-cm spacing, P = .01). VPDR(D90/D10) for PBS was higher than for VMAT (2-cm spacing, P =.004; 3-cm spacing, P = .002). Normal tissue V5 was lower for PBS than for VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Normal tissue mean dose was lower with PBS than with VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Two patients treated using PBS GRID and assessed with pretreatment QACT scans demonstrated robust PVDR, VPDR(D90/D10), and organs-at-risk doses. Conclusions: The PEDR was significantly higher for PBS than VMAT plans, indicating lower target edge dose. Normal tissue mean dose was significantly lower with PBS than VMAT. PBS GRID may result in lower normal tissue dose compared with VMAT plans, allowing for further dose escalation in patients with bulky disease.

Simple Summary: The lattice technique is a particular form of spatially fractionated radiation therapy, which was demonstrated to be safe and effective for treating advanced cancers. Bulky tumor disease is difficult to treat. In this clinical scenario, radiotherapy has a role in the palliation of symptoms. The lattice technique allows high doses to be delivered within tumor masses. Combining lattice delivery with IMRT/VMAT to bulky tumors offers optimal symptom control and could emerge as the best therapeutic option in this setting of patients. Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative "metabolism-guided" lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher 18F-FDG uptake (>75% SUV max) and areas with lower 18F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10–27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: "Metabolism-guided" lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting. [ABSTRACT FROM AUTHOR]

Type II uterine tumors often present with very large, necrotic tumor burden in the uterus that leads to dilation and effacement of the cervix. In patients with this presentation, conventional hysterectomy poses a much greater challenge as the ureters are composed of the mass of the tumor and are at an increased risk for injury. Given this surgical challenge, many of these patients may begin with neoadjuvant chemo-radiation. However, these treatment modalities are associated with significant toxicity and negatively impact patient quality of life. Therefore, we describe a minimally invasive robotic surgical approach that aims to optimize quality of life without sacrificing prognosis. Outcomes of 4 patients are presented. [ABSTRACT FROM AUTHOR]

For fast, safe, and effective management of large and bulky (≥8 cm) non‐resectable tumors, we have developed a conebeam CT‐guided three‐dimensional (3D)‐conformal MLC‐based spatially fractionated radiation therapy (SFRT) treatment. Using an in‐house MLC‐fitting algorithm, Millennium 120 leaves were fitted to the gross tumor volume (GTV) generating 1‐cm diameter holes at 2‐cm center‐to‐center distance at isocenter. SFRT plans of 15 Gy were generated using four to six coplanar crossfire gantry angles 60° apart with a 90° collimator, differentially weighted with 6‐ or 10‐MV beams. A dose was calculated using AcurosXB algorithm, generating sieve‐like dose channels without post‐processing the physician‐drawn GTV contour within an hour of CT simulation allowing for the same day treatment. In total, 50 extracranial patients have been planned and treated using this method, comprising multiple treatment sites. This novel MLC‐fitting algorithm provided excellent dose parameters with mean GTV (V7.5 Gy) and mean GTV doses of 53.2% and 7.9 Gy, respectively, for 15 Gy plans. Average peak‐to‐valley dose ratio was 3.2. Mean beam‐on time was 3.32 min, and treatment time, including patient setup and CBCT to beam‐off, was within 15 min. Average 3D couch correction from original skin‐markers was <1.0 cm. 3D MLC‐based SFRT plans enhanced target dose for bulky masses, including deep‐seated large tumors while protecting skin and adjacent critical organs. Additionally, it provides the same day, safe, effective, and convenient treatment by eliminating the risk to therapists and patients from heavy gantry‐mounted physical GRID‐block—we recommend other centers to use this simple and clinically useful method. This rapid SFRT planning technique is easily adoptable in any radiation oncology clinic by eliminating the need for plan optimization and patient‐specific quality assurance times while providing dosimetry information in the treatment planning system. This potentially allows for dose‐escalation to deep‐seated masses to debulk unresectable large tumors providing an option for neoadjuvant treatment. An outcome study of clinical trial is underway. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit–risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models. Methods: We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed. Results: We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system. Conclusions: PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system's role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it. [ABSTRACT FROM AUTHOR]

Background and PurposeMost locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop “in-field.” Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients.Materials and MethodsWe analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups.ResultsIn the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS.ConclusionOur initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT.

Background and Purpose: Most locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop "in-field." Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients. Materials and Methods: We analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups. Results: In the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS. Conclusion: Our initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxygen-guided radiotherapy is a new modality for cancer irradiation. Spatially Fractionated Radiation Therapy allows the treatment of hypoxic tumor areas with high radiation doses. Radiotherapy enhances immunotherapy effectiveness. Abscopal and bystander effects are important radiobiological issues. The aim of this paper was to analyze the recent development of a particular kind of radiation therapy that is based on high-dose delivery in small areas within large tumor masses. We performed a narrative review of the radiobiological rationale behind a potential benefit by using these techniques combined with immunotherapy and employing personalized target definition according to hypoxic areas. Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the "oxygen-guided radiation therapy" (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT. [ABSTRACT FROM AUTHOR]

Objectives The clinical outcomes of patients treated with spatially fractionated GRID radiotherapy (SFGRT) for bulky tumors of the head and neck at a single institution were evaluated retrospectively. Endpoints of interest included tumor response, symptom improvement, treatment tolerance, and adverse events. Methods Institutional review board approval was obtained prior to study initiation. The institutional database was queried for patients with tumors of the head and neck treated with SFGRT between August 2007 and April 2015. Medical records of identified patients were reviewed for treatment details and clinical endpoints of interest. SFGRT was delivered in one fraction of 15 gray (Gy) or 20 Gy; 6 megavolt (MV) or 18 MV photon beams were passed through a multileaf collimator (MLC)-based or brass GRID template. All patients had a planned course of conventionally-fractionated external beam radiotherapy (EBRT) to begin on the day following SFGRT delivery. Results Twenty-one consecutive patients meeting study criteria were identified. The most common tumor histology was squamous cell carcinoma. Median patient age was 59 years (range 13 - 83 years); median maximum tumor dimension was 9.5 centimeters (cm) (range 5.0 - 25.0 cm). Fifteen patients (71.4%) completed their full course of EBRT. Twelve patients were treated with palliative intent for local tumor symptoms, of which 54.5% experienced some degree of symptom improvement. Of nine patients treated with curative intent, 44.4% achieved a clinical complete response (CR). Concurrent chemotherapy was administered in 12 patients, with all patients being treated having definitively received chemotherapy. Radiation Therapy Oncology Group (RTOG) grade three or higher skin toxicity occurred in five patients; no grade five events were reported. Conclusions Our institutional experience suggests that SFGRT is a feasible treatment option for the palliative or definitive management of large tumors of the head and neck. In combination with EBRT, SFGRT can provide timely symptom management and improve patient quality of life in the palliative setting. In the definitive setting, the addition of chemotherapy to SFGRT and EBRT can result in an excellent clinical response. Treatment toxicity was found to be within an acceptable range. When considering SFGRT for patients with these challenging presentations, careful patient selection is needed to identify those who will likely tolerate a full course of EBRT following SFGRT, as these patients are most likely to receive maximal benefit from SFGRT treatment. More data on the feasibility and efficacy of this radiation modality will be helpful for continued optimization of SFGRT delivery and patient selection., Competing Interests: The authors have declared that no competing interests exist.