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Purpose: To compare plan quality among photon volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT) with robustness using three different proton beam delivery systems with various spot size (σ) ranges: cyclotron-generated proton beams (CPBs) (σ: 2.7-7.0 mm), linear accelerator proton beams (LPBs) (σ: 2.9-5.5 mm), and linear accelerator proton mini beams (LPMBs) (σ: 0.8-3.9 mm) for the treatment of head and neck (HN) cancer with bilateral neck irradiation., Methods: Ten patients treated for oropharynx cancer with bilateral neck irradiation were planned using CPBs, LPBs, LPMBs, and VMAT. The homogeneity index (HI), mean body dose, and defined volumetric doses for selected critical organs-at-risk (OARs) were compared. Set-up uncertainties of ±3 mm and ± 3.5% range uncertainties were included in robust evaluation using V 95%Rx  > 95% (Volume that covers 95% of the target volume at 95% of the prescription (Rx) dose) to high dose and low dose CTV volumes (CTV&#95;70 Gy and CTV&#95;56 Gy). VMAT and proton plans were compared in terms of OAR doses and mean body dose only. Homogeneity Indices were compared among IMPT plans in addition to OAR doses. The Wilcoxon signed-rank test was used to evaluate statistical differences between evaluation metrics for VMAT plans and all proton plan types., Results: OAR dose metrics were improved by 2% to 30% from CPB plans to LPB or LPMB plans. Compared to photon VMAT plans, all OAR doses except for mandible dose metrics were improved by 2% to 53% for all proton plans. The mean body dose was also improved by 7.5% from CPB to LPB and by 10.8% from CPB to LPMB. In addition, the mean body dose was also improved by 44% from VMAT to CPB, by 48% from VMAT to LPB, and by 50% from VMAT to LPMB plans. Compared to CPB plans, HI was significantly better (p < 0.05) for the LPB and LPMB plans. HI also improved considerably from VMAT to CPB, LPB, and LPMB. For both CTV&#95;70 Gy and CTV&#95;56 Gy, average robust evaluation across all worst-case scenarios was slightly better for CPB plans, with an average of V 95%Rx of the CTV&#95;70 Gy of 97.6% ± 1.22%, followed by 97.2% ± 1.31% and 97.2% ± 1.35% for LPB and LPMB plans, respectively. Robustness for CTV&#95;56 Gy showed comparable robustness across all proton plan types, with an average V 95%Rx of 97.4% ± 0.87% for CPB, 97.4% ± 1.21%, and 97.5% ± 1.08% for CPB, LPB, and LPMB plans, respectively., Conclusion: With decreased spot size, the LPB and LPMB are excellent alternatives to VMAT and CPB therapy and can significantly reduce the dose to normal tissue., (© 2025 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

To compare proton plans (IMPT) to VMAT plans and intercompare proton plans using 3 different spot sizes with robustness: cyclotron-generated proton beams (CPB) (σ: 2.7-7.0 mm), linear accelerator proton beams (LPB) (σ: 2.9-5.5 mm), and linear accelerator proton mini beams (LPMB) (σ: 0.9-3.9 mm) for the treatment of early-stage lung cancer. Twenty-two lesions from a total of twenty patients with early-stage lung cancer, originally treated with SBRT, were replanned using CPBs, LPBs, LPMBs, and VMAT using the same treatment planning system and dose calculation algorithm. The average intensity projected CTs (AIP-CT) were used for planning and 3D robust optimization was used for all proton plans. Conformity index (CI), homogeneity index (HI), R 50 , lung V 20   Gy , and mean lung dose were compared among all proton plan types and with VMAT plans. Set-up uncertainties of ±5 mm and ±3.5% range uncertainty were included in the IMPT robust optimization and evaluation, using V 100%Rx > 98% of the ITV. The Wilcoxon signed-rank test was used to evaluate statistical differences between VMAT plans and all proton plan types. When compared to VMAT plans, all proton plans generally show improvement in CI, HI, Lung V 20   Gy , Mean lung dose, and R 50 . The LPMB plans showed the most improvement from VMAT plans. Comparison between CPB and linear accelerator proton plans showed statistical significance (p < 0.05). R 50 and mean lung dose for the CPB, LPB and LPMB plans were 3.6 ± 0.9, 3.1 ± 0.8 and 2.6 ± 0.6; 2.2 ± 1.1 Gy, 1.9 ± 1 Gy and 1.6 ± 0.9 Gy, respectively (p < 0.05). The mean R 50 and mean lung dose from the VMAT plans were 4.1 ± 0.4 and 3.8 ± 2 Gy, respectively. The V 20   Gy (%) of lung and mean lung dose were improved across all proton plans when compared with those of VMAT plans. When evaluated for robustness in the worst-case scenario at V 100%Rx of the ITV > 98%, average ITV coverage of 98.6 ± 0.3%, 98.6 ± 0.6%, and 98.9 ± 0.6% were achieved for CPB plans, LPB plans, and LPMB plans, respectively. With decreased spot size, the LPB and LPMB plans are excellent alternatives to VMAT and cyclotron-generated proton plans with reduced dose to normal tissue and improved plan quality for early-stage lung cancer treatments., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare plan quality among photon volumetric arc therapy (VMAT), Gamma Knife, and three different proton beam modalities., Methods: Fifty-five brain lesions from 20 patients were planned with three different proton spot size ranges of cyclotron-generated proton beams, CPBs (spot size σ: 2.7-7.0 mm), linear accelerator proton beams, LPBs (σ: 2.9-5.5 mm), and linear accelerator proton minibeams, LPMBs (σ: 0.9-3.9 mm), with and without apertures and compared against photon VMAT and Gamma Knife plans. Dose coverage to each lesion for each proton and photon plan was set to 99% of the GTV receiving the prescription (Rx) dose. All proton plans used ±2 mm setup uncertainty and ±2% range uncertainty in robust evaluation to achieve V 100%Rx > 95% of the GTV. Apertures were applied to proton beams irradiating tumors <1 cm 3 volume and located <2.5 cm depth. Conformity index (CI), gradient index (GI), V 12 Gy , V 4.5 Gy , and mean brain dose were compared across all plan types. The Wilcoxon signed rank test was utilized to determine statistical significance of dosimetric results compared between photon and proton plans., Results: When compared to CPB generated plans, average CI and GI were significantly better for the LPB and LPMB plans. Aperture-based IMPT plans showed improvement from Gamma Knife for all dosimetric metrics. Aperture-based IMPT plans also showed improvement in all dosimetric metrics for shallow tumors (d < 2.5 cm) when compared with non-aperture-based plans., Conclusion: The LPB and LPMB stand as excellent alternatives to CPB or photon therapy and significantly increase the preservation of normal tissue., Competing Interests: Authors’ disclosure of potential conflicts of interest Dr Farr reports collaborative research grant with Advanced Oncotherapy (AVO) — IRB number 19-1180, DATA1119: Using proton mini-beams to improve SBRT/SRS plan conformity, Board member at large for the AAPM Journal of Medical Physics, stock in Advanced Oncotherapy, plc and he is the Chief Clinical Officer of A.D.A.M SA Director General. Dr Xia reports collaborative research grant with Advanced Oncotherapy (AVO) — IRB number 19-1180, DATA1119: Using proton mini-beams to improve SBRT/SRS plan conformity. Other authors have nothing to disclose., (© 2024 Old City Publishing, Inc.)

Gonorrhea is a sexually transmitted disease caused by Neisseria gonorrhoeae and has a wide clinical spectrum that can range from asymptomatic to disseminated disease. Most women with gonorrhea are asymptomatic and if left untreated, it can lead to serious complications like pelvic inflammatory disease (PID) and infertility. Disseminated gonococcal infection (DGI) is usually characterized by dermatitis, tenosynovitis, and septic arthritis but rarely can also cause bacteremia, endovascular infections, osteomyelitis, and meningitis. Gonococcal bacteremia is regarded as a disseminated disease and is typically associated with infection of the mucosal surfaces such as the urethra, endocervix, and pharynx. This report, to the best of our knowledge, presents a case of DGI associated with a mediport catheter in a patient with breast cancer without any history of gonococcal symptoms. She was monogamous and denied any history of sexually transmitted infections. The patient presented with fever and chills associated with pain and purulent discharge from the mediport catheter site. The mediport catheter was removed, and antibiotics were initiated. Both blood and wound cultures grew N. gonorrhoeae . She completed a 10-day course of ceftriaxone and improved clinically with complete remission of her symptoms. A review of the literature on the reported cases of DGI associated with bacteremia and endovascular infections is also presented., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Malik et al.)

Purpose: Prior in silico simulations propose that Temporally Feathered Radiation Therapy (TFRT) may reduce toxicity related to head and neck radiation therapy. In this study we demonstrate a step-by-step guide to TFRT planning with modern treatment planning systems., Methods: One patient with oropharyngeal cancer planned for definitive radiation therapy using intensity-modulated radiation therapy (IMRT) techniques was replanned using the TFRT technique. Five organs at risk (OAR) were identified to be feathered. A "base plan" was first created based on desired planning target volumes (PTV) coverage, plan conformality, and OAR constraints. The base plan was then re-optimized by modifying planning objectives, to generate five subplans. All beams from each subplan were imported onto one trial to create the composite TFRT plan. The composite TFRT plan was directly compared with the non-TFRT IMRT plan. During plan assessment, the composite TFRT was first evaluated followed by each subplan to meet preset compliance criteria., Results: The following organs were feathered: oral cavity, right submandibular gland, left submandibular gland, supraglottis, and OAR Pharynx. Prescription dose PTV coverage (>95%) was met in each subplan and the composite TFRT plan. Expected small variations in dose were observed among the plans. The percent variation between the high fractional dose and average low fractional dose was 29%, 28%, 24%, 19%, and 10% for the oral cavity, right submandibular, left submandibular, supraglottis, and OAR pharynx nonoverlapping with the PTV., Conclusions: Temporally Feathered Radiation Therapy planning is possible with modern treatment planning systems. Modest dosimetric changes are observed with TFRT planning compared with non-TFRT IMRT planning. We await the results of the current prospective trial to seeking to demonstrate the feasibility of TFRT in the modern clinical workflow (NCT03768856). Further studies will be required to demonstrate the potential benefit of TFRT over non-TFRT IMRT Planning., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a robust immune surveillance program elicited by T cells, which is further enhanced by the addition of immune-checkpoint blockade. Combining YKL-5-124 with anti-PD-1 offers significant survival benefit in multiple highly aggressive murine models of SCLC, providing a rationale for new combination regimens consisting of CDK7 inhibitors and immunotherapies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess three advanced radiation therapy treatment planning tools on the intensity-modulated radiation therapy (IMRT) quality and consistency when compared to the clinically approved plans, referred as manual plans, which were planned without using any of these advanced planning tools., Materials and Methods: Three advanced radiation therapy treatment planning tools, including auto-planning, knowledge-based planning, and multiple criteria optimization, were assessed on 20 previously treated clinical cases. Three institutions participated in this study, each with expertise in one of these tools. The twenty cases were retrospectively selected from Cleveland Clinic, including five head-and-neck (HN) cases, five brain cases, five prostate with pelvic lymph nodes cases, and five spine cases. A set of general planning objectives and organs-at-risk (OAR) dose constraints for each disease site from Cleveland Clinic was shared with other two institutions. A total of 60 IMRT research plans (20 from each institution) were designed with the same beam configuration as in the respective manual plans. For each disease site, detailed isodoseline distributions and dose volume histograms for a randomly selected representative case were compared among the three research plans and manual plan. In addition, dosimetric endpoints of five cases for each site were compared., Results: Compared to the manual plans, the research plans using advanced tools showed substantial improvement for the HN patient cases, including the maximum dose to the spinal cord and brainstem and mean dose to the parotid glands. For the brain, prostate, and spine cases, the four types of plans were comparable based on dosimetric endpoint comparisons., Conclusion: With minimal planner interventions, advanced treatment planning tools are clinically useful, producing a plan quality similarly to or better than manual plans, improving plan consistency. For difficult cases such as HN cancer, advanced planning tools can further reduce radiation doses to numerous OARs while delivering adequate dose to the tumor targets., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)