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Advances in the immunological pharmaceuticals, such as checkpoint inhibitors and agonists, have positive implications for the future of the radiotherapy abscopal response. A once rare phenomenon, whereby distant nonirradiated tumor sites regressed after radiotherapy alone, may become more common when combined with the immune modulating agents. Radiotherapy can increase neoantigen expression, increased tumor PD-L1 expression, increase MHC class I expression, reverse exhausted CD8 T cells and increase tumor-infiltrating tumors within the tumor microenvironment. These changes in the tumor and the tumor microenvironment after radiotherapy could potentiate responses to anti-CTL-4, anti-PD-L1/PD-1 and other immunotherapy agents. Thus, advances in checkpoint inhibitors have increased interest in re-evaluation of the role of conventional radiotherapy approaches on the immune system. We reviewed newer nonconventional approaches such as SBRT-PATHY, GRID, FLASH, carbon ion and proton therapy and their role in eliciting immune responses. We believe that combining these novel radiation methods may enhance the outcome with the newly US FDA approved immune modulating agents.

Postmastectomy pain syndrome (PMPS) or breast conservation surgery (BCS) pain syndrome could be long-term and lead to disability and impairment on body and social function. The pain syndromes are not uncommon in breast cancer patients. It can affect social, psychological, physical and behavioral aspects of a patient. Surgery, radiation, chemotherapy and psychological factors can all contribute to the development of pain syndromes. Axillary dissection is a strong predictor for pain development. Pain medications, ganglion blocks are typically given to the patient for management. Integrative medicine such as acupuncture and psychological management methods are promising modalities in the management arsenal. In this study, we summarized the up-to-date literature to elucidate the etiology, risk factors and management strategies for PMPS.

Spatially Fractionated Radiation therapy (SFRT) has a history of over 100 years. The principle of SFRT is distinctive from the standard radiation approaches, as it treats the total tumor with a non-uniform dose, effectively treating the tumor while staying within normal tissue tolerance of the surrounding structures. Historically, SFRT is frequently used to treat bulky malignant tumors with a high radiation dose in the stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) dose range (10–20 Gy per fraction) using megavoltage x-ray beams. The application of SFRT, historically known as GRID therapy, has produced dramatic relief of severe symptoms, significant objective regression, above average local control rates and minimal toxicity in palliative settings [1]. The advancement of physics and technology has provided more techniques to deliver SFRT. Some understandings of radiobiology and immunology have been generated from studies of SFRT. These promising clinical results have generated a renewed interest in this technique at many centers in the United States and internationally. A series of novel application of SFRT in clinical trials are being anticipated in the near future. Here, we summarize the history, the present and the future of SFRT. As current reviews of SFRT are lacking, we present a comprehensive review of SFRT and its clinical implications.

Background Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC. Materials and methods Sixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients). Results Median follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options. Conclusion SBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials. Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 31/19.

Purpose/Objective(s) Accurate contouring of the target is very important in radiation therapy treatment planning. Unlike most other cancers where the radiation target occupies a small area of an organ, prostate cancer treatment involves the irradiation of the entire prostate. This study evaluates the quality of prostate contours generated from a deep learning segmentation (DLSEG) model. Materials/Methods A total of 23 prostate cancer patients who did not underwent prostatectomy was randomly selected. The original contours used clinically was carefully quality checked and revised when necessary by one expert radiation oncologist (RO) and regarded as the ground truth (GT). Two additional ROs were invited to perform manual contouring of the prostate from scratch. Auto contours (labelled as AI) generated by a research version of DLSEG was then compared with those from manual delineations. A paired t-test was employed for statistical comparison. A comparative geometric analysis of the manual and automatic delineations was performed to quantify the multi-observer delineation variability, including dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD). Results Using GT contour as reference, the contours from three additional RO achieved an average of 0.81 ± 0.04 for DSC, 0.60 ± 0.16cm and 0.21 ± 0.05cm for HD95 and MSD, respectively. In contrast, AI contours achieved an average of 0.83 ± 0.05 for DSC, 0.60 ± 0.18cm and 0.21 ± 0.07 cm for HD95 and MSD, respectively. No statistical difference was found for the delineation accuracy between the three observers (P > 0.05). AI contours were considered to have similar performance to the three human experts with all geometric metrics (P > 0.05). Conclusion The DLSEG model for prostate contouring tested demonstrates similar performance in terms of accuracy compared with expert ROs.

Aim A single-institution, retrospective study was performed to investigate potential techniques to minimize radiation exposure to the testicles during heterotopic ossification (HO) prophylaxis. We report the impact of split-beam technique (SBT) and different photon energies on the total dose of radiation received by the testicles during prophylaxis of HO. Materials and methods Between 2008 and 2010, we identified 64 patients with traumatic acetabular fractures who underwent surgery followed by radiation therapy (RT) without testicular shielding. Postoperative RT was delivered within 72 h in a single fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to patient refusal. All patients underwent 3-D RT planning in which the testicles were contoured as a region of interest and dose-volume histograms (DVH) were generated. Additional treatment planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV) to study the effects of these maneuvers on the delivered dose to the testicles. Results In reviewing the DVH, it was noted that the mean dose delivered to the testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430). When SBT was utilized, a significant reduction in the mean (44%) and maximum (47%) doses delivered to the testicles was noted. Further reductions in the mean (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV) beams. The radiation doses to the testicles from the CT simulation and the two portal images were estimated to be 4 and 1.5 cGy, respectively. Conclusion Low-dose prophylactic RT to prevent HO around the hip causes a low, but likely biologically meaningful, radiation dose to be delivered to the testicles. This dose could be further reduced by using a medial SBT and photon energies above 6 MV. Testicular shielding should be offered to all male patients receiving such RT. In addition, all patients should be informed about the consequences of testicular radiation as part of their informed consent.

Background/aim Scattered radiation during radiotherapy (RT) directed at the hip joint poses concerns about ovarian function in patients of reproductive age. Here, we report the impact of using a split-beam technique (SBT) and different photon energies on the total ovary dose during radiation prophylaxis of heterotopic ossification (HO). Patients and methods This was a single-institution, retrospective study of 32-patients with traumatic acetabular fractures (TAF). All underwent surgery followed by CT-based-RT within 72 h in a single fraction of 700 cGy. Ipsilateral (IL) and contralateral (CL) ovaries (OV) were contoured separately and dose volume histograms (DVH) generated. Additional planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6-18 MV) to investigate the difference in ovary dose among these maneuvers. Results The median Mean-dose delivered to ILOV was 59 cGy and the median Max-dose was 177 cGy. CLOV median Mean-dose was 6 cGy and median Max-dose was 10 cGy. SBT at the medial edge of the field led to a 27% and 22% dose reduction in the median Mean and Max. doses, respectively, to ILOV; 9% and 5% reduction was seen in the median Mean and Max. doses, respectively, to CLOV. Higher photon energies (10-18 MV) led to an additional 28% and 16 % reduction in median Mean and Max. doses, respectively, to ILOV when compared to those from 6 MV. The CLOV median Mean dose was reduced by 18% and the Max. dose was reduced by 12%. Conclusion A biologically significant radiation dose is delivered to the ovaries during HO radiation prophylaxis at the hip joints. Ipsilateral ovarian dose could be reduced by half and contralateral by one-quarter by using CT-based treatment planning with a medial SBT and photon energies above 6 MV. We suggest using no more than 10 MV to minimize neutron contamination. Those techniques should be the standard of care as it provides a reliable method for minimizing the radiation dose to the ovaries, consequently, maximizing female fertility preservation during HO radiation prophylaxis. All female patients in childbearing age should be fully informed about ovarian radiation exposure and possible temporary alteration in ova production and morphology.

Purpose. Transoral robotic surgery (TORS) has increased in popularity in the management of squamous cell carcinoma of the head and neck. However, TORS does not address the neck or retropharyngeal nodes (RPN). In the current report, we highlight the impact of the lack of adjuvant radiotherapy on RPN recurrence after TORS.Materials and Methods. A 58-year-old Caucasian male presented with squamous cell carcinoma of the head and neck of unknown primary. He was offered radiotherapy as a definitive management for clinical stage T0N2aM0, stage IVA, but he opted to left neck dissection. Follow-up PET-CT scan revealed recurrence in the left base of tongue and right level II lymph node. He was offered radiotherapy which he declined and opted to TORS and right neck dissection. Follow-up PET-CT scan showed recurrence in left RPN for which he underwent salvage concurrent chemoradiotherapy to 70 Gy.Results. After a followup of 9 months from the date of salvage chemoradiotherapy completion, the patient is with no evidence of disease.Conclusions. TORS followed by adjuvant radiotherapy seems reasonable in the context of squamous cell carcinoma of the head and neck due to the odds of RPN involvement. Further reports are warranted to optimize post-TORS adjuvant treatment.

Purpose To compare the short-term toxicity and dosimetry of tandem and ring (TR), and tandem and ovoid (TO) applicators in treatment of gynecologic malignancy. Material and methods Following pelvic external beam radiation therapy (EBRT), a total of 52 computed tomography-based plans from 13 patients with cervical cancer (FIGO IB2-IIIB) were evaluated for HDR brachytherapy. Prescription was 7 Gy to the ICRU point A for four weekly fractions. Gastrointestinal and genitourinary toxicities were evaluated. Clinical target volume (CTV) and organs at risk were delineated on CT scans. Bladder, rectum, and sigmoid mean doses and D2cc were calculated. Treatment time and irradiated tissue volume were compared. Percent of CTV receiving 100% (CTV100%) of the prescribed dose as well as the percent of the prescription dose covering 90% of the CTV (D90) were evaluated. Results Gastrointestinal and genitourinary toxicities were not different between TO and TR applicators. No significant differences in the dose to the right and left point A, or the left point B were observed. TO delivered a higher dose to right point B. Organs at risk doses were similar between the two applicators, except mean rectal dose was lower for TO applicator. Overall, TO treats a larger tissue volume than TR. Mean treatment time was shorter for TR. Tumor coverage (D90 and CTV100%) was equivalent between TO and TR applicators. Conclusion Although TO treats a larger tissue volume than TR, short-term toxicities and tumor coverage are similar. Long-term clinical outcomes will be elucidated with longer follow up period.

Purpose/Objectives We observed a number of patients who developed Lhermitte’s sign (LS) following radiation to the head and neck (H/N), since instituting volumetric modulated arc therapy (VMAT). We aimed to investigate the incidence of LS following VMAT-based RT without chemotherapy, and determine the dosimetric parameters that predict its development. We explored whether the role of inhomogeneous dose distribution across the spinal cord, causing a “bath-and-shower” effect, explains this finding. Methods and Materials From 1/20/2010–12/9/2013, we identified 33 consecutive patients receiving adjuvant RT using VMAT to the H/N without chemotherapy at our institution. Patients’ treatment plans were analyzed for dosimetric parameters, including dose gradients along the anterior, posterior, right, and left quadrants at each cervical spine level. Institutional Review Board approval was obtained. Results 5 out of 33 (15.2%) patients developed LS in our patient group, all of whom had RT to the ipsilateral neck only. LS patients had a steeper dose gradient between left and right quadrants across all cervical spine levels (repeated-measures ANOVA, p = 0.030). Within the unilateral treatment group, LS patients received a higher mean dose across all seven cervical spinal levels (repeated-measures ANOVA, p = 0.046). Dose gradients in the anterior-posterior direction and mean doses to the cord were not significant between LS and non-LS patients. Conclusions Dose gradients along the axial plane of the spinal cord may contribute to LS development; however, a threshold dose within the high dose region of the cord may still be required. This is the first clinical study to suggest that inhomogeneous dose distributions in the cord may be relevant in humans. Further investigation is warranted to determine treatment-planning parameters associated with development of LS.

Purpose and Objective(s): To investigate the advantages of volumetric treatment planning in HDR brachytherapy for cervical carcinoma compared to standardized loading based on 2-D planning techniques. Materials and Methods: Our institution uses volume-based 3-D planning for each tandem and ovoid (T&O) insertion for HDR brachytherapy in the treatment of advanced cervical carcinoma. Here, we attempt to define the benefits of this approach. We re-planned 48 CT-based treatment plans on 12 patients (treated in our facility between February, 2009 and February, 2010) using a commonly used 2-D standard HDR loading of the T&O. All patients had received 4 fractions of 6.5 Gy or 5 fractions of 5.5 Gy to point H or A. The following organs at risk (OARs) were contoured: rectum, bladder, sigmoid, and small bowel. Our customized planning approach required the adjustment of source dwell times and positions to keep doses to the OARs below 80% of the prescription dose. The standardized HDR planning, however, bases the loading time on the length of the tandem. The dwell time for each tandem source position is the same. The dwell time multipliers for the ovoids were 0.33, 0.665 and 1.0, proportionate to the 2 cm, 4 cm, and 6 cm tandem length, respectively. The dose to the highest 2 cc (D2cc) of the OARs were also determined and analyzed. Results: There was a marked change in the value and location of the D2cc for all OARs from one HDR session to the next in both the standard and customized plans. When the data for the 48 plans were analyzed together, there were no significant differences between the customized plans and the standardized plans. However, when data for the individual plans were analyzed, 35% of the 2-D based plans did not meet our treatment planning objectives. Conclusion: Using customized plans for HDR T&O brachytherapy did not always reduce the doses to the rectum, bladder, sigmoid, and small bowels compared to the standardized plans. The dose to the small bowel could be up to 15% higher than the dose to point H or A in the standard plans indicating that customized plans may be superior to the standardized ones for the treatment of patients where this dose is critical.

OBJECTIVE: Meningeal melanocytomas are rare entities that range from benign and well-differentiated lesions with a favorable prognosis to higher-grade lesions that may undergo malignant transformation with subsequent CNS dissemination. Transition from a meningeal melanocytoma to primary CNS melanoma is particularly rare with only a handful of cases reported. Systemic spread of a transformed meningeal melanocytoma, an exquisitely rare occurrence, is, to the best of our knowledge, reported in only three cases. Here we report the case of a woman who initially presented with multifocal meningeal melanocytomas with subsequent rapid transformation, diffuse CNS seeding, and systemic metastases. CLINICAL PRESENTATION AND MANAGEMENT: A 43 year-old woman presented with headaches, nausea, and vomiting for two months with negative GI work-up. She experienced a syncopal episode with CT and MRI brain scans showing 3 dural-based lesions involving the foramen magnum, fourth ventricle, and right CPA. The patient underwent STR of the lesions; the anterior lesion was inaccessible. Pathology reported a melanocytoma with malignant features. A negative dermatology and ophthalmology work-up were performed. The patient received post-operative radiotherapy (50.4 Gy) to the posterior fossa. Six months following surgery she presented with new neurological symptoms, and MRI of the neuroaxis showed new leptomeningeal enhancement within the cerebellum, thoracic spine, and supratentorially. With neuro-oncology input, she was started on Temodar and underwent palliative spinal RT. Unfortunately she continued to experience pain, and follow-up MRI showed new intrathecal C-spine nodules. Abdominal imaging revealed multiple lung and liver metastases, with biopsy of a 7-cm liver lesion revealing malignant melanoma. The patient unfortunately continued to deteriorate and succumbed to her disease approximately 9 months following diagnosis. CONCLUSION: Meningeal melanocytomas are rare tumors that are not only challenging to diagnose, but challenging to clinically predict and manage. This case illustrates these challenges and the multidisciplinary response needed to optimize outcomes.

To evaluate the locoregional control and treatment toxicity of patients with pleomorphic adenoma after resection with close or positive margins followed by postoperative radiation therapy (PORT).Between 2002 and 2011, twenty-one patients underwent PORT at the Mount Sinai Beth Israel Medical Center for pleomorphic adenoma of the parotid with close or positive margins. Four out of the 21 patients (19%) had recurrent lesions. The median dose was 57.6 Gy (range 55.8-69.96) delivered at 1.8-2.12 Gy/fraction. Treatment and follow-up data were retrospectively analyzed for locoregional control as well as acute- and late-treatment toxicities. Actuarial survival analysis was also performed.Twelve women and 9 men with a median age of 46 (26-65) at PORT were included in this study. Eighty-one percent of the cohort had positive resection margins while 19% had close margins. At a median follow-up of 92 months, 19/21 patients (90%) had locoregional control. Two patients who failed had primary lesions which recurred locally, and initially had positive margins. The two recurrences occurred at 8 months and 12 months. Acute Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicities were experienced by 11 (52%) and 4 (19%) patients, respectively, while 2 (10%) experienced late RTOG grade 1 toxicities. No patients experienced any grade 2-4 late toxicities. Actuarial survival was 100%.PORT for patients with pleomorphic adenoma of the parotid gland after resection with close or positive margins results in excellent locoregional control and low treatment-related morbidity.

Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context.Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%.At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%).RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.

To report long-term outcomes for HIV-positive patients who underwent radiation therapy (RT) for benign lymphoepithelial cysts (BLEC) of the parotid glands.In this single institution retrospective study of HIV-associated BLEC of the parotids, the medical records of 37 HIV-positive patients who were treated with RT between 1987-2012 were reviewed. Patients were stratified into two groups; group A consisted of 15 patients (40.5%) who received a total dose of ≤18Gy, with a median dose 10 Gy (range 8-18Gy), and group B consisted of 22 patients (59.5%) who received a total dose of 24 Gy. In addition to dosing information, additional patient data were collected, including demographics, HAART compliance, follow-up, and re-treatment status.The median age at the time of treatment was 41 (range=7-70) years. With a median follow-up of 35 (range=12-75) months for the entire cohort, the complete response (CR) and partial response (PR) rates were 35% and 8%, respectively. All but one of 15 patients in Group A (lower total dose) eventually experienced local failure with the re-emergence of parotid hypertrophy. Among the patients in group B (higher total dose of 24 Gy), 55%, 13%, and 32% experienced CR, PR, and LF, respectively. Median times to failure in groups A and B were 7 and 20 months, respectively (p0.0001). Similarly, logistic regression test revealed the higher dose to be associated with better response rate (i.e. CR or PR) (p0.0001), which was also statistically significant (p=0.03) after adjusting for confounding variables (age, race, gender, HAART use, and fractionation).A total dose of 24 Gy continues to be recommended for durable cosmetic control of BLEC of the parotid glands that is associated with HIV-seropositivity.

To investigate the impact of definitive radiation therapy (RT) in the management of early glottic cancer on clinical RT-induced dysphagia (RID) and carotid vasculopathy (RICV).This is a single-institution retrospective study. From January 1997 to 2010, 253 patients, with early glottic cancer, underwent RT with (60)Co or LINAC-6 MV photons. RT fields with wedge pair and daily 5-mm bolus were applied in all patients treated with 6-MV photons to avoid under-dose of the anterior laryngeal structures. The whole larynx (LX), pharyngeal constrictors (PCs), and carotid arteries (CA) were contoured and dose-volume histograms (DVHs) were generated to assess the delivered dose. The median age of patients was 65 years (range; 28-93), Caucasians were 80%, males were 87%, and 23% had T2 lesions.After a median follow-up of seven years (range; 1.5-12), the median dose and fraction size delivered to the LX were 63 and 2.25 Gy, respectively. The mean doses to the LX, PC, and CA were 57 Gy delivered to 34 cm(3), 54 Gy to 15 cm(3), and 60 Gy to 4 cm(3), respectively. The LX, PC and CA V60 and V65 were (77 and 71), (70 and 52) and (84 and 51), respectively. Patients with acute dysphagia grades 1, 2, and 3 or more were 81, 19%, and zero, respectively; none had clinically RID or RICV.Small-volume RT up to 67.5 Gy at 2.25 Gy per fraction, is not a predictor of RID or RICV. Separate delineation of the aforementioned critical structures, as well as others, may better identify dose tolerances to maintain function and further prioritize the importance of structures in RID and RICV.