The Current Role of Radiation in the Management of Cholangiocarcinoma-A Narrative Review.

Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors.

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy.

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review.

PURPOSE: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation. METHODS AND MATERIALS: We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy. RESULTS: Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT. CONCLUSIONS: In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.

Detection of Circulating Tumor DNA After Stereotactic Ablative Radiotherapy in Patients With Unbiopsied Lung Tumors (SABR-DETECT).

For patients with stage I/IIA non-small-cell lung cancer (NSCLC), surgical resection is the standard treatment. However, some of these patients are not candidates for surgery or refuse a surgical option. Definitive stereotactic ablative radiotherapy (SABR) is a standard approach in these patients. Approximately 15% of patients undergoing SABR for localized NSCLC will experience a recurrence within 2 years. Furthermore, many of these patients are deemed appropriate for SABR without a tissue diagnosis, based on the likelihood of malignancy which can be calculated by validated models. A liquid biopsy, detecting ctDNA, would be useful in early detection of recurrences, and documenting a cancer diagnosis in patients without a biopsy. This is a multi-institutional study enrolling patients with suspected stage I/IIA NSCLC and a pretreatment likelihood of malignancy of ≥60% using the validated models for patients without a tissue diagnosis, in cohort 1 (n = 45). The second cohort will consist of biopsied patients (n = 30-60). SABR will be delivered as per risk-adapted protocol. Plasma will be collected for ctDNA analysis prior to the first fraction of SABR, 24 to 72 hours after first fraction, and at 3, 6, 9, 12, 18, and 24-months. The patients will be followed up with imaging at 3, 6, 9, 12, 18, and 24-months. The primary objective is to assess whether a cancer detection liquid biopsy platform can predict recurrence of NSCLC. The secondary objectives are to assess the impact of SABR on detection rates of ctDNA in patients undergoing SABR and to correlate ctDNA positivity and pretreatment probability of malignancy (NCT05921474).

The role of thoracic consolidative radiotherapy in the setting of immunotherapy in extensive stage small cell lung cancer.

The improvement in treatment strategies and outcomes in small cell lung cancer (SCLC) has lagged behind other cancers. The addition of immune checkpoint inhibitors (ICIs), durvalumab and atezolizumab, to the platinum-based chemotherapy in frontline setting has improved the survival in extensive stage SCLC, (ES-SCLC), albeit modestly, and is now the new standard of care. Prior to advent of immunotherapy into the therapeutic armamentarium in ES-SCLC, consolidative thoracic radiotherapy (TRT) was associated with improved thoracic control and survival outcomes. In the era of ICIs, the role of TRT is not well defined, chiefly because TRT was not incorporated in any immunotherapy trials, secondly due to concerns regarding the increased risks of pneumonitis, and finally uncertain magnitude of benefit with this combined approach. In principle, radiation can increase in the immunogenicity of tumor and hence the activity of immune checkpoint blockade, thereby increasing efficacy both locally and distantly. Such an approach has been promising in non-small cell lung cancer with ICIs improving outcomes after concurrent chemoradiation, but remains unanswered in ES-SCLC. It is, thus, possible that the modest improvement in survival by addition of ICIs to chemotherapy in ES-SCLC can be further improved by the incorporation of consolidative TRT in selected patients. Several early phase trials and retrospective studies have suggested that such an approach may be feasible and safe. Prospective trials are ongoing to answer whether adding radiation therapy to chemoimmunotherapy will improve outcomes in ES-SCLC.

Impact of Oncology Drug Review Times on Public Funding Recommendations.

New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal-Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000-1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs.

'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review.

Antibody-Drug conjugates (ADCs) are a relatively new class of drugs with a promise to improve the outcomes in specific cancers. By delivering the cytotoxic agent to tumor cells expressing specific antigens, ADCs achieve a better therapeutic index and more potency. ADCs have been approved for several hematological and solid malignancies, including breast, urothelial and gastric carcinoma. Recently, trastuzumab deruxtecan (TDXd) was the first ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer (NSCLC). Many promising ADCs are in the pipeline for clinical development in non-small cell lung cancer, including sacituzumab govitecan, patritumab deruxtecan, datopotamab deruxtecan and tusamitamab ravtansine. There is a hope that these drugs would cater to the unmet need of specific patient populations, including patients with currently untargetable mutations. We hope these drugs, e.g., TROP2 targeted ADCs, will also give more options for therapy in NSCLC to improve outcomes for patients. In this comprehensive review, we will be discussing the recent evidence including targets, efficacy and the safety of newer ADC candidates in NSCLC. We will also briefly discuss the specific toxicities, novel biomarkers, overcoming resistance mechanisms, challenges and the way forward, as these new ADCs and combinations find a way into the clinical practice.

Survival of Persons Living With HIV/AIDS: A Multicentric Study From India.

BACKGROUND: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program. METHODS: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years. RESULTS AND DISCUSSION: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005). CONCLUSION: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality.

Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With Advanced Non-small Cell Lung Cancer Harboring Activating EGFR Mutations: A Systematic Review and Meta-analysis.

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non-small cell lung cancer. We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced non-small cell lung cancer harboring activating EGFR mutations, in comparison to EGFR TKIs alone. The electronic databases were searched for relevant randomized trials between 2000 and 2022. The primary endpoints were overall survival (OS) and progression-free survival. Secondary endpoints included objective response rate (ORR), disease control rate, and grade ≥3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. A total of 1528 patients from 8 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 37% (HR=0.63; 95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant difference in objective response rate or disease control rate between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension being the most significantly increased AEs. This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves progression-free survival, with no OS benefit, and increases AEs. Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results.

Supportless Lattice Structure for Additive Manufacturing of Functional Products and the Evaluation of Its Mechanical Property at Variable Strain Rates.

This study proposes an innovative design solution based on the design for additive manufacturing (DfAM) and post-process for manufacturing industrial-grade products by reducing additive manufacturing (AM) time and improving production agility. The design of the supportless open cell Sea Urchin lattice structure is analyzed using DfAM for material extrusion (MEX) process to print support free in any direction. The open cell is converted into a global closed cell to entrap secondary foam material. The lattice structure is 3D printed with Polyethylene terephthalate glycol (PETG) material and is filled with foam using the Hybrid MEX process. Foam-filling improves the lattice structure's energy absorption and crash force efficiency when tested at different strain rates. An industrial case study demonstrates the importance and application of this lightweight and tough design to meet the challenging current and future mass customization market. A consumer-based industrial scenario is chosen wherein an innovative 3D-printed universal puck accommodates different shapes of products across the supply line. The pucks are prone to collisions on the supply line, generating shock loads and hazardous noise. The results show that support-free global closed-cell lattice structures filled with foam improve energy absorption at a high strain rate and enhance the functional requirement of noise reduction during the collision.

Differential effect of body mass index (BMI) on outcomes of patients treated with docetaxel in prostate cancer - An exploratory analysis.

OBJECTIVE: There are contradictory data on differential effect of docetaxel based on BMI in patients with breast and prostate cancer. We performed an exploratory analysis to determine if the benefit of docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) is modified by BMI. METHODS: We performed a post hoc analysis of the data retrieved from the ENTHUSE M1C study. BMI (kg/m2) was categorized as: 18.5 to <25 as lean; 25 to <30 as overweight; and ≥30 as obese. Cox regression models were constructed to determine the impact of BMI on progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 466 patients were eligible for the current analysis. The median PFS was 7.3, 7.7 and 8.4 months (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.81 to 1.06; P = 0.261) in lean, overweight and obese patients. The median OS was 16.6, 20.1 and 21.4 months (HR, 0.75; 95% CI, 0.63 to 0.89; P = 0.002) for lean, overweight and obese patients. After adjusting for baseline and tumor characteristics, there was no association of BMI with PFS (overweight, HR, 0.89; 95% CI, 0.71 to 1.13; P = 0.353; obese, HR, 0.86; 95% CI, 0.66 to 1.13; P = 0.277) while overweight (HR, 0.68; 95% CI, 0.51 to 0.89; P = 0.006) and obese (HR, 0.59; 95% CI, 0.41 to 0.83; P = 0.003) patients had significantly better OS compared with lean patients. CONCLUSIONS: There was no effect of BMI on PFS in patients with mCRPC receiving docetaxel. Interestingly, overweight and obese patients had a longer OS compared with lean patients, which is in contradiction to a recent study in breast cancer; and warrants further investigation.

Autologous Hematopoietic Stem Cell Transplant: A Potential Option for Relapsed Pediatric Acute Myeloid Leukemia With Lack of Matched Sibling Donor and Resource Challenge.

Though allogeneic hematopoietic stem cell transplant (HSCT) is standard for relapsed pediatric acute myeloid leukemia, often it may not be accessible due to donor unavailability and resource limitations. We retrospectively analyzed outcomes of 26 children (mean age: 10.9±4.5 y) who underwent autologous HSCT in complete remission 2. Three-year event-free survival and overall survival were 50.1±10.7% and 63.3±9%, respectively; with 1 treatment-related death and 46% relapse rate. Notwithstanding the retrospective study design and somewhat favorable patient characteristics, the outcomes are comparable with those of other series and our own allogeneic HSCT data. Autologous HSCT is a potential alternative to allogeneic HSCT, especially in countries with poorly maintained donor registries.

Neoadjuvant Systemic Chemotherapy in Sebaceous Gland Carcinoma of the Eyelid: A Retrospective Study.

There are sparse data on neoadjuvant systemic chemotherapy (NACT) in eyelid sebaceous gland carcinoma (SGC). The aim of this study was to evaluate efficacy and outcomes with NACT in eyelid SGC. We retrospectively analyzed 8 patients who received platinum-based NACT. The median number of cycles per patient was 4 (range, 3-5). The mean percentage reduction of tumor diameter after NACT was 71% (range, 30-100%). Two patients had a radiological complete response (CR). After NACT, surgical treatment for residual tumor was performed in 5 cases. One patient had a pathological CR and is recurrence free for 11 years. After a mean follow-up period of 44.5 months (range, 9-109), tumor recurrence occurred in 4 cases. Among these 4 cases, 3 were rechallenged with the same regimen and all responded. Systemic NACT has a role in eyelid SGC, downstages the tumor, and allows less aggressive and organ-sparing surgeries, warranting a prospective study.

Trabectedin in Advanced Sarcomas-Experience at a Tertiary Care Center and Review of Literature.

Background There is sparse literature on trabectedin in advanced soft-tissue sarcomas from developing world. It would be interesting to know about use and outcomes of trabectedin in Indian patients. Method In a retrospective study, consecutive patients treated with trabectedin from 2016 to 2019 were analyzed. Patients with L-sarcomas were treated at a dose of 1.5 mg/m 2 , while those with translocation-related sarcomas were treated at a dose of 1.2 mg/m 2 as a 24-hour infusion through peripherally inserted central catheter line. From July 2019, infusions were administered through an ambulatory elastomeric pump, while before that patients were admitted for 24 hours. We used SPSS version 23.0 for statistical calculation. Result A total of 20 patients received trabectedin with a total of 116 infusions. The median age was 46 years (range: 22-73 years). The male ( n = 11, 55%) and female patients were almost equal ( n = 9, 45%). Thirteen patients (65%) had Eastern Cooperative Oncology Group Performance Status 1. Majority of the patients had leiomyosarcoma ( n = 8, 40%); remaining comprised of liposarcoma (3, 15%), translocation-related sarcomas excluding myxoid liposarcoma ( n = 8, 40%) and others ( n = 1,5%). Most common site was extremity ( n = 11, 55%) followed by retroperitoneal ( n = 3, 15%), visceral ( n = 3, 15%), and others ( n = 3,15%). Median number of previous lines received was 2 (range: 0-4). Median number of trabectedin cycles received was 4 (range: 1-17). Best response assessed was stable disease ( n = 10, 50%), progressive disease ( n = 6, 30%), partial response ( n = 1, 5%), and not assessed in 3 patients. After a median follow-up of 19 months, median progression-free survival was 4 months. Conclusion In this heavily treated population (composed of L-sarcomas and translocation-related sarcomas) with many patients with poor performance status, the outcome with trabectedin is in synchrony with literature. However, the need of 24-hour admission might deter quality of life. Elastomeric pump seems to be a reasonable alternative to admission and can be a breakthrough in administering trabectedin, especially in developing countries.

Avapritinib in advanced gastrointestinal stromal tumor: case series and review of the literature from a tertiary care center in India.

The therapeutic landscape in advanced gastrointestinal stromal tumor has evolved. Avapritinib and ripretinib have now been approved by the US FDA for platelet-derived growth factor alpha D842V-mutant and refractory gastrointestinal stromal tumor patients, respectively. Here we report five patients who have been on avapritinib under an expanded access program. Response assessment was available for four patients - a partial response in two patients and stable disease in one, while one patient had progressive disease. Though preliminary results of the VOYAGER trial have shown less activity of avapritinib and no significant difference in progression-free survival when compared with regorafenib, avapritinib may show some clinical benefit in a subset of patients refractory to approved therapies. We share our experience of five cases, with clinical benefit in three. We believe avapritinib should be further evaluated in clinical trials.

Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma.

BACKGROUND: Chordoma is a rare, slow growing and locally aggressive mesenchymal neoplasm with uncommon distant metastases. It is a chemo-resistant disease with surgery and radiotherapy being the mainstay in treatment of localized disease. In advanced disease imatinib has a role. We report a case of metastatic sacral chordoma with symptomatic and radiological response to erlotinib post-progression on imatinib. CASE PRESENTATION: A 48-year-old male with a sacral chordoma underwent partial sacrectomy followed by post-operative radiotherapy. Upon recurrence he received palliative radiotherapy to hemipelvis and was offered therapy with imatinib. However, the disease was refractory to imatinib and he was started on treatment with erlotinib-showing a partial response on imaging at two months. He is currently doing well at 13 months since start of erlotinib. CONCLUSIONS: As seen in previously reported cases, erlotinib is a therapeutic option in advanced chordoma, even in imatinib refractory cases and thus warrants exploration of its therapeutic role in prospective clinical trials.

A case report of Kaposiform haemangioendothelioma; response with propranolol and steroids.

BACKGROUND: Kaposiform haemangioendothelioma is a rare vascular tumor and may involve skin, deep soft tissue or bone. It is a locally aggressive tumor usually seen in infants. Here we report a case of kaposiform hemagioendothelioma in a child who responded to propranolol and steroids. CASE PRESENTATION: A 3-year-old male child presented with a swelling below his right knee with characteristic violet skin lesion. There was no evidence of Kasabach-Merritt phenomenon. After no improvement with several attempts at debridement and anti-tubercular treatment; a diagnosis of Kaposiform Haemangioendothelioma was reached on the basis of overall clinical picture and histology. The child was treated with propranolol and steroids and had an excellent clinical response and a near complete resolution on imaging at 5 months. CONCLUSIONS: These cases are often misdiagnosed and despite a delay in diagnosis have good outcomes with appropriate multimodality management. This case highlights the unique and typical characteristics of kaposiform haemangioendothelioma.

Utility and safety of maintenance chemotherapy in advanced non-small cell lung cancer across various performance status categories: real-world experience.

Maintenance chemotherapy (MC) with pemetrexed is a commonly used strategy in nonsquamous non-small cell lung cancer. However, most of the available evidence is from subjects with good performance status (PS), while data on the real-world utility and safety of this strategy in subjects with various categories of PS is limited. We performed a retrospective analysis of multicentric data of 3 centers from India. All patients with advanced nonsquamous non-small cell lung cancer who received MC with pemetrexed after induction chemotherapy were included. Subjects were divided into 2 groups based on baseline Eastern Cooperative Oncology Group score before initiation of induction chemotherapy as good PS (<2) and poor PS (≥2). Progression-free survival, overall survival, and toxicity were assessed in the study population. A total of 290 subjects were included in the study, of whom a significant proportion (n = 104, 35.9%) had poor PS. Survival was better in subjects with good PS as compared to those with poor PS (1-year progression-free survival: 43.5% vs 29.8%, P = 0.021; 1-year overall survival: 61.8% vs 48.1%, P = 0.023). Grade 3/4 toxicity was observed in 14.5% of subjects during MC and was not different between both groups (P = 0.287). Renal dysfunction was more common in subjects who received ≥10 cycles of MC (10.7% vs 4.2%, P = 0.040). MC with pemetrexed appeared to be beneficial and safe in the real-world setting regardless of the baseline PS. However, survival benefit was more pronounced in subjects with good PS at baseline. Renal dysfunction was more frequently encountered in subjects who received prolonged MC.

Supportless Lattice Structures for Energy Absorption Fabricated by Fused Deposition Modeling.

Additively manufactured cellular structures represent a promising engineering design concept for making customized products where user-specific mechanical properties are required. One of the major challenges in the additive manufacturing (AM) process is removal of unwanted support structures from the lattice. The support structure consumes extra material, printing time, and energy for manufacturing. Postprinting, it needs extensive postprocessing work to remove it from the lattice structure chemically or mechanically. In the case of flexible materials such as thermoplastic polyurethane (TPU), removing the support structure from the lattice is very difficult with the material extrusion process. In this article, a new type of a shell-shaped lattice structure inspired by sea urchin (SU) morphology is designed. This lattice can be additively manufactured by material extrusion processes such as fused deposition modeling (FDM) without requiring any support structures. The mechanical properties of the proposed structure, such as stiffness and energy absorption during loading and unloading, have been evaluated as they are important for cushioning. The compressive results indicate that the stiffness property is almost twice as high compared with the benchmarked, bending-dominated, body-centered cubic (BCC) lattice structure of the same relative density and ethylene vinyl acetate (EVA) foam. Energy absorption is almost equal to the BCC lattice and 20% better than EVA foam. Last, a predictive model on stiffness behavior and energy return was developed to facilitate a systematic way to select optimal densities of the SU lattice structure for energy-absorbing applications. Visual inspection has also revealed that there is no sagging or failure of the lattice, which reduced the manufacturing time and postprocessing time, saving a significant amount of material without compromising on quality. Supportless lattice printing was also validated by printing the specimen with a different FDM printer and TPU filament. A possible application for supportless lattice structures can be for AM of customized shoe midsoles at low cost, ski boots, tires, automotive crush boxes, or any other energy-absorbing structures.