Post Radiation Research Articles

Radiation dose to the cochlea and its association with sensorineural hearing loss in head and neck cancer-A prospective study

AimTo determine the effect of cochlear dose on sensorineural hearing loss in patients with head and neck cancer treated by radiotherapy and chemoradiotherapy. Materials and methodA two-year longitudinal study was conducted on 130 subjects with various head and neck malignancies who were receiving radiotherapy or chemoradiation. 56 patients received only radiotherapy while 74 patients received concurrent chemoradiation five days a week at a dose of 66–70 Gy. They were categorized as having a radiation dose to the cochlea of <35 Gy, <45 Gy or >45 Gy. Pre- and post-therapy audiological evaluation was done using a Pure-tone audiogram, distortion product otoacoustic emission, and impedence. Hearing thresholds were measured at frequencies up to 16,000 Hz. ResultsOut of 130 patients 56 received RT alone and 74 received CTRT. There was statistically significant (p value <0.005) difference in Pure-tone audiometry assessment in both the RT and CTRT groups between subjects who received more than and <45 Gy of radiation to the cochlea. There was no significant difference in distortion product otoacoustic emission assessment between patients who received >45 Gy and <45 Gy radiation to the cochlea. Comparison between subjects who received radiation dose of <35 Gy and >45 Gy revealed significant results in the degree of hearing loss (p value <0.005). ConclusionWe observed that patients who received >45 Gy of radiation had more sensorineural hearing loss compared to patients who received <45 Gy. A cochlear dose of <35 Gy is associated with significantly lower hearing loss compared to higher doses. We would like to conclude by emphasizing the importance of regular audiological assessments prior to and post radiotherapy and chemoradiotherapy, with regular follow-ups encouraged over a longer period to improve the quality of life in patients with head and neck malignancy.

Small Round Blue Cell Tumours of the Sinonasal Area: Our 5 year Experience in a Tertiary Care Centre in India.

Purpose: The main purpose of this study is to understand the characteristics and management of sinonasal small round blue cell tumors and also to emphasise the role of immunohistochemistry in their diagnosis and on the outcomes after endoscopic/open excision in these patients. Methods: This is a retrospective study conducted at a tertiary care referral centre in India which included 38 patients with sino nasal for a period of 5 years. All the patients were evaluated clinically and radiologically. All cases were confirmed diagnostically with histopathological examination and immunohistochemistry following surgical excision either by endoscopic or open approach. Some of the cases underwent post operative radiotherapy. Results: In our study, among 176 cases diagnosed with Sino nasal malignancies, 38 (21.6%) cases were diagnosed with sinonasal small round blue cell tumors with male to female ratio 1.4:1. Most common histopathological type among all the sinonasal small round blue cell tumors that presented to us was esthesioneuroblastoma i.e., 8 (21%) patients followed by pituitary macroadenoma in 7(8.4%) patients. Other types are undifferentiated squamous cell carcinoma 10(13.1%), craniopharyngioma 8(10.5%), lymphoma 3(7.9%), synovial/spindle cell sarcoma, malignant melanoma and adenocarcinoma 1(2.6%) each. Schwannoma, rhabdomyosarcoma, neuroendocrine carcinoma and neurofibroma 2 (5.2%) each. Conclusion: Sinonasal small round blue cell tumors are extremely rare tumours. Histopathological diagnosis with immunohistochemistry is characteristic of various tumors and is conclusive for diagnosis. Knowledge of these tumor entity is essential as early diagnosis helps in further management in preventing spread to vital structures and improving outcome. Most of the tumors have a multimodality treatment approach which includes surgical excision, radiotherapy and chemotherapy.

Total ionizing dose effect of bulk and SOI P-FinFET with linear workfunction modulation technology

The effect total ionizing dose on a linear gate workfunction modulated SOI P-FinFET is analyzed and compared with the bulk P-FinFET. This technique improves the device electrostatic integrity for pre and post radiation condition. A decade improvement in IOFF is obtained for both the bulk and proposed devices. Moreover, both the SOI devices offer 35% and 29% less subthreshold swing for pre-rad condition. After irradiation trap charges are accumulated in oxide and semiconductor/insulator interfaces, which makes threshold more negative. The linear gate workfunction modulation gives more Vth for both devices. At high radiation of 2000 krad dose proposed SOI device shows 39% more threshold voltage as compared to LGWM bulk P-FinFET. The maximum Vth shift is observed in single workfunction bulk P-FinFET. Based on the simulation results, the proposed SOI P-FinFET is proved to be better TID tolerant and reliable.

PD-0168 Impact of tumor nuclei size variation for post radiotherapy recurrence outcome of GYN patients

PD-0168 Impact of tumor nuclei size variation for post radiotherapy recurrence outcome of GYN patients

PD-0164 The value of post Radiotherapy PSA dynamics for prostate cancer risk stratification models

PD-0164 The value of post Radiotherapy PSA dynamics for prostate cancer risk stratification models

PO-2127 Linear quadratic model is not a valid predictive model for post radiation clonogenic cell survival

PO-2127 Linear quadratic model is not a valid predictive model for post radiation clonogenic cell survival

"Pharyngolaringeal Neoplasm Treated with Surgery and Radiotherapy – Squamous Cell Carcinoma with Sarcomatoid Dedifferentiation – Clinical Case"

"Sarcomatoid carcinoma is a rare and aggressive form of squamous cell carcinoma (SCC). It is a biphasic tumor that has been shown to be a dedifferentiated monoclonal form of classic squamous cell carcinoma. The factors that contribute to proliferation of SCC to sarcomatoid carcinoma are not precisely known but some studies revealed the importance of anterior radiation therapy. This case report describes a 62-year-old man, heavy smoker and alcohol drinker diagnosed with laryngeal neoplasm. The pathological diagnosis was well-differentiated SCC of the piriform sinus. Surgery was performed and the pathology report revealed medium differentiated SCC, pT4aN1M0. The patient underwent external radiotherapy (RT) with 66Gy/tumour bed in 33 fractions. At 4 months post RT the clinical exam revealed tumor recurrence near the tracheal stoma. A second surgery was performed and the pathology diagnosed a recurrence of SCC with sarcomatoid-looking areas, with two surgical margins being invaded by the tumor. Postoperative computer tomography (CT) of the neck showed no evidence of macroscopic disease. The next treatment used was chemotherapy with 4 cycles of carboplatin paclitaxel but soon after, an inoperable locoregional recurrence was diagnosed and he started treatment with Nivolumab followed by rapid locoregional progression. Squamous cell carcinoma with sarcomatoid dedifferentiation is a rare histology of laryngeal cancer, with an aggressive behavior that requires intense treatment and follow-up."

Uncommon Presentation of an Uncommon Disease: Stroke-like Migraine Attacks after Radiation Therapy in a Patient with Sudden Onset Expressive Aphasia and Cryptogenic Fevers (P3-5.029)

<h3>Objective:</h3> To present a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome accompanied by fever. <h3>Background:</h3> SMART syndrome is an uncommon condition that presents as migraines with focal neurologic deficits in patients who have undergone brain radiation. This syndrome can present decades after completion of radiation therapy and therefore represents a unique diagnostic challenge. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 26-year-old man with a history of myxopapillary ependymoma status post whole brain radiation therapy 15 years prior presented with 3 days of headaches, sudden onset aphasia, and fevers. Initial exam was significant for severe expressive aphasia with only 1–2 words of speech production. Head CT was unremarkable. CT angiography demonstrated slightly decreased arborization of the distal MCA territory vessels in the left cerebral hemisphere but was otherwise unremarkable. Patient was empirically treated for CNS infection with antimicrobial therapy. CSF analysis was unremarkable, as was the remainder of his infectious workup. Long term EEG monitoring showed focal slowing in the left hemisphere but did not show any epileptiform activity. MRI was completed with arterial spin labeling (ASL) sequence, which showed increased perfusion in the left cerebral hemisphere, consistent with SMART syndrome. Patient’s exam gradually improved over the following week. He followed up in clinic 6 weeks later and his symptoms had significantly improved. He was almost back to baseline. Fevers and headaches had completed resolved. <h3>Conclusions:</h3> This case of SMART syndrome has the typical findings of sudden onset migraines and focal neurologic deficits in a patient who previously underwent brain radiation therapy. Our case was unique in that the patient had fevers of unknown origin; a phenomenon that has only been reported in one prior case. The use of MRI perfusion or ASL can aid in the diagnosis; in this case showing increased perfusion over the affected cerebral hemisphere. <b>Disclosure:</b> Dr. Gill has nothing to disclose. Dr. Gill has nothing to disclose. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Akcea Therapeutics. Gino Mongelluzzo has nothing to disclose.

Early Post Radiation Neuropathy: Complex Pathogenesis Including Microvasculitis and Tumor Spread (P14-8.001)

<h3>Objective:</h3> To describe patients with early radiation-induced peripheral nerve injury and investigate potential pathogenic mechanism(s). <h3>Background:</h3> Radiation-induced neuropathy typically occurs up to decades after radiation from neural fibrosis with insidious, painless progressive weakness. Reports of early radiation-associated neuropathies are lacking. <h3>Design/Methods:</h3> Patient cases labeled as “radiation neuropathy” were electronically retrieved from our electromyography (EMG) and Mayo Data Explorer databases between January 2014 to August 2022. Inclusion criteria included neural deficits within 6 months of radiation, EMG testing, and available follow-up nerve imaging. <h3>Results:</h3> Twenty-two patients (9 female, mean age 63 years [range 34–84]) were identified with a history of squamous (n=6), prostate (n=5), breast (n=3), rectal (n=2), hematologic (n=2), and other (n=4) cancers. Average radiation dose was 4491 cGy (range 1000–7208). Time to symptom onset averaged 1.9 months (range 0–4). Pre-radiation chemotherapy occurred in most (n=16). All neuropathies occurred in the same radiation territory, but most neuropathies (n=17) occurred distal to the radiation site. EMG-confirmed neuropathies included radiculopathies (n=10), brachial and lumbosacral plexopathies (n=10), and mononeuropathies (n=2). EMG myokymia was seen in few (n=6). Patients reported primarily painful paresthesias (n=18) and weakness (n=18). Clinical courses were monophasic (n=8), progressive (n=8), static (n=2), and unclear without follow-up (n=4). Follow-up neural MRI did not suggest infiltrative disease (n=21), but based on tumor location and progressive course, microscopic infiltration was suspected. Two patients had nerve biopsies showing prominent inflammation around epineural microvessels with vessel wall injury (microvasculitis). One biopsy revealed neoplastic spread of rectal squamous cell cancer. Steroid burst therapy was attempted in 6 patients; 5 reported benefits, and 4 had monophasic courses. <h3>Conclusions:</h3> Early-onset post radiation neuropathies having pain and monophasic courses are supported by steroid response and biopsy-confirmed microvasculitis to have an inflammatory-immune mechanism. Exclusion of infiltrative cancer and an idiosyncratic radiation injury with progressive course are important to consider. <b>Disclosure:</b> Dr. Skolka has nothing to disclose. Dr. Uhm has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Zai Lab. Dr. Ma has nothing to disclose. Dr. Santilli has nothing to disclose. Mr. Meiling has nothing to disclose. Dr. Sandroni has nothing to disclose. Dr. Staff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stem Cell Research &amp; Therapy. Dr. Pinto has nothing to disclose. Dr. Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea/Ionis. Dr. Klein has a non-compensated relationship as a Klein with Neurology Journal that is relevant to AAN interests or activities.

Brachytherapy using radiation carriers: Case series

Brachytherapy reduces the post radiation sequalae as the dose required is lower than external beam radiation therapy (EBRT) and limits the area of exposure. This case report outlines two different patients managed by fabrication of radiation carrier prosthesis for the duration of the brachytherapy.

The predictive role of baseline pulmonary function test in lung carcinoma patients for radiation-induced lung toxicity treated with conformal radiation therapy

Abstract Introduction: Radiation-induced lung toxicity (RILT) is a major concern in patients who receive radiation to thorax. The purpose of the study was to evaluate the changes of pulmonary function tests (PFTs) in lung carcinoma patients treated with three-dimensional conformal radiation therapy (3-D CRT) and relation RILT with dosimetric and nondosimetric factors. Methods: This was a prospective observational study which included 65 patients of lung carcinoma treated with 3-D CRT. PFTs were assessed before the radiotherapy and at third and sixth month post-radiation therapy. Radiation pneumonitis (RP) was graded according to National Cancer Institute Common Toxicity Criteria (CTCAE) version 4.0. Results: Majority of patients already had poor lung function before commencing the radiotherapy. There was a modest decrease in pulmonary function after radiation therapy with (3-D CRT). Postradiotherapy, at third month, eight patients (12%) and at the sixth month, 16 patients (25%) were observed with Grade II RP. At the third month, the nondosimetric factors, age &gt;65 years (P = 0.027) and pretreatment Diffusion capacity of the Lung for Carbon monoxide (DLCO) 60% (P = 0.03) were significantly related to grade ≥ II Radiation pneumonitis (RP). Among dosimetric factors, mean lung dose ≥20 Gy (P = 0.001) and volume receving 20Gy ≥35% (P = 0.05) were significantly related to grade ≥ II RP. These factors were also related to grade ≥ II RP at the sixth month with a significant P value. Conclusion: There is a progressive decrease in pulmonary function after (3-D CRT) in lung carcinoma patients. The study suggested that the baseline PFT may be utilized for the identification of high-risk patients for RILT before starting the radiotherapy in lung carcinoma.

MR-guided ultrasound-stimulated microbubble therapy enhances radiation-induced tumor response

High intensity focused ultrasound (HIFU) systems have been approved for therapeutic ultrasound delivery to cause tissue ablation or induced hyperthermia. Microbubble agents have also been used in combination with sonication exposures. These require temperature feedback and monitoring to prevent unstable cavitation and prevent excess tissue heating. Previous work has utilized lower power and pressure to oscillate microbubbles and transfer energy to endothelial cells in the absence of thermally induced damage that can radiosensitize tumors. This work investigated whether reduced acoustic power and pressure on a commercial available MR-integrated HIFU system could result in enhanced radiation-induced tumor response after exposure to ultrasound-stimulated microbubbles (USMB) therapy. A commercially available MR-integrated HIFU system was used with a hyperthermia system calibration provided by the manufacturer. The ultrasound transducer was calibrated to reach a peak negative pressure of − 750 kPa. Thirty male New Zealand white rabbits bearing human derived PC3 tumors were grouped to receive no treatment, 14 min of USMB, 8 Gy of radiation in a separate irradiation cabinet, or combined treatments. In vivo temperature changes were collected using MR thermometry at the tumor center and far-field muscle region. Tissues specimens were collected 24 h post radiation therapy. Tumor cell death was measured and compared to untreated controls through hematoxylin and eosin staining and immunohistochemical analysis. The desired peak negative pressure of − 750 kPa used for previous USMB occurred at approximately an input power of 5 W. Temperature changes were limited to under 4 °C in ten of twelve rabbits monitored. The median temperature in the far-field muscle region of the leg was 2.50 °C for groups receiving USMB alone or in combination with radiation. Finally, statistically significant tumor cell death was demonstrated using immunohistochemical analysis in the combined therapy group compared to untreated controls. A commercial MR-guided therapy HIFU system was able to effectively treat PC3 tumors in a rabbit model using USMB therapy in combination with radiation exposures. Future work could find the use of reduced power and pressure levels in a commercial MR-guided therapy system to mechanically stimulate microbubbles and damage endothelial cells without requiring high thermal doses to elicit an antitumor response.

The Patient's perspective: A review of the results from a radiotherapy patient experience survey in the North-West of England

IntroductionA patient experience survey was undertaken for patients completing radiotherapy at the three Northwest of England Radiotherapy Providers. MethodsA previously reported National Radiotherapy Patient Experience Survey was adapted and undertaken in the Northwest of England. Quantitative data was analysed to establish trends. Frequency distribution was applied to appraise the number of participants selecting each of the pre-determined responses. Thematic analysis of free text responses was conducted. ResultsThe questionnaire received 653 responses from the 3 providers across seven departments. Thematic analysis revealed 3 themes; logistics, information and operational. ConclusionThe results indicate that the majority of patients are satisfied with their treatment and care. Patients' responses indicate areas for improvements. Expectancy theory states that an individual's satisfaction is related to the difference between expected service and the service received. Consequently, when reviewing services and developing improvement it is important to understand patients' expectations. This regional survey starts to capture what people receiving radiotherapy expect from the service and the professionals delivering their treatment. Implications for practiceThis survey responses make a case for reviewing the information provision pre and post radiotherapy. This includes clarifying the understanding of consent for treatment including the intended benefits and potential late effects. There is an argument to offer information sessions prior to radiotherapy to achieve more relaxed and informed patients. A recommendation from this work is for the radiotherapy community undertake a national radiotherapy patient experience survey, facilitated via the 11 Radiotherapy ODNs. A national radiotherapy survey has multiple benefits to inform improvements in practice. This includes benchmarking services against national averages. This approach is aligned with the principles of the service specification in terms of reducing variation and increasing quality.

C-POST protocol update: A Phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post surgery and radiation therapy in patients with high-risk cutaneous squamous cell carcinoma

C-POST protocol update: A Phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post surgery and radiation therapy in patients with high-risk cutaneous squamous cell carcinoma

Abstract P1-10-15: Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study

Abstract Purpose/Objective(s): The purpose of this paper is to report the dosimetric effects of conscious sparing of contralateral lobe of thyroid gland in carcinoma breast patient receiving locoregional radiation by tangential beam Intensity Modulated radiotherapy technique. Materials/Methods: Treatment plans of 20 Ca Breast patients, who received post mastectomy adjuvant locoregional radiotherapy, were evaluated. Since October 2021 we adopted a department protocol of conscious sparing of contralateral thyroid in breast radiotherapy. 10 of these had conscious sparing of contralateral thyroid (group A) whereas 10 of old plans were evaluated when C/L thyroid were not given constraints &amp; are being passively spared due to location on contralateral/non treatment side of neck (group B). Treatment planning was done using tangential beam (6 MV) IMRT in Eclipse 13.7 TPS in all of these patients. All of these patients received treatment to chest wall &amp; SCF. RTOG contouring guidelines were followed in all the patients. Prescription Dose was 40Gy in 15# for both groups. The best treatment plans were selected ensuring 95% PTV dose coverage and acceptable dose to OARs. Uniform contouring, plan optimization &amp; evaluation protocols were followed for all of these patients. Results: The mean thyroid volume in group A is 4.30cc &amp; in group B is 3.99cc which is not statistically different (P value -0.639) The mean dose of thyroid in group A is 7.98Gy whereas in group B it is 17.00Gy which is spastically significant (P value – 0.000003). Comparison of mean dose to contralateral lobe (in Gy) between the two groups Groups No. Mean ± SD ‘t’ value P value Thyroid dose with constraint 10 7.98±1.46 -6.702, df=18 0.000003* Thyroid dose without constraint 10 17.00±3.99 Unpaired ‘t’ test applied. P value = 0.000003, Significant Conclusion: OARs present on contralateral side are passively spared due to the location. This often results in a tendency of not actively prescribing constraints to these. This study emphasizes that conscious sparing of contralateral Thyroid lobe can further reduce the dose to significant levels. This reduction can preserve thyroid function further. Further clinical trials are required to corroborate this dosimetric gain with clinical thyroid function preservation. Citation Format: Manish Chomal, Minaal Iyer, Ananth Kalimurthy, Joshua Sahay, Sushanta Banik. Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-15.

Abstract P5-07-08: Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer

Abstract BACKGROUND: HER2-positive breast cancers, which accounts for 20% of breast cancers, is associated with aggressive clinical behavior and inferior survival. The approval of HER2 targeted therapy has changed the landscape of this disease and has reduced disease recurrence by 50% and has improved survival by 33%. (1) However, cardiotoxicity is a well-recognized adverse event associated with HER2-targeted therapies. Adjuvant trastuzumab emtansine (TDM1) is the current standard of care for patients with residual breast cancer after neoadjuvant HER2-targeted therapy. TDM1 is associated with a risk of cardiotoxicity defined as a decline in left ventricular ejection fraction (LVEF). In a pooled analysis of data from seven metastatic breast cancer trials with TDM1, the incidence of cardiac events such as congestive heart failure (CHF), cardiac ischemia, cardiac arrhythmia or grade 1/2 LVEF drop was 3.37%. Adjuvant breast radiation (RT) is routinely offered for patients at high risk for recurrence. Breast RT is also associated with long-term increased risk of cardiac disease more than 10 years after RT. The HERA trial which studied use of adjuvant trastuzumab showed that rates of cardiotoxicity were higher in patients receiving concurrent RT with trastuzumab (left sided &amp;gt; right sided breast cancer) compared to those who did not receive adjuvant RT, although not statistically significant. In the multivariate analysis, no treatment or baseline cardiovascular risk factors were strongly correlated with LVEF, but radiation therapy showed a borderline correlation (adjusted HR, 1.258; 95% CI, 1.00-1.58; P = .049). The risk of cardiotoxicity with concurrent TDM1 and RT has not been well studied. With increasing use of TDM1 in the adjuvant setting, it is important to understand the cardiotoxic effects of combination therapy in early-stage breast cancer. METHODS: We undertook a review of our clinical database to identify patients who received adjuvant TDM1 with concurrent RT for Stage I-III breast cancer from 1/2020 to 01/2022. Clinical parameters including age, date of diagnosis, history of cardiac disorders, echocardiogram findings, radiation dose, final pathologic stage and molecular subtypes of cancer were extracted. All patients had ejection fraction to monitor cardiac fraction. Global longitudinal strain (GLS), which is a more sensitive and reproducible indicator of cardiac dysfunction than LVEF, was also collected, if available. RESULTS: Of 32 patients identified in our retrospective analysis, two patients (6%) developed a drop in ejection fraction post radiation. Median age of patients was 57y. Majority of the patients were Caucasian (44%) followed by Hispanic (28%). 19 (60%) patients had right sided breast cancers and 13(40%) patients had left sided cancers. The mean pre-radiation ejection fraction was 60% and post radiation was 61%. Using paired t-testing, there was no statically significant difference in ejection fraction after radiation (p=0.343). Comparative GLS measurements were available for 16 patients and there was no statical difference with concurrent radiation (p=0.18). All patients tolerated radiation with mostly grade 2 skin dermatitis except four patients who had grade 3 skin dermatitis. One patient had to discontinue radiation early given grade 3 skin dermatitis. CONCLUSION: This institutional review of 32 patients suggests that adjuvant TDM1 with concurrent RT did not result in a significant change in ejection fraction or GLS. Most patients tolerated radiation without significant skin toxicities. One of the limitations of the study is the small sample size. A larger study should look at more broader conclusions; however this data has strong clinical implications. Cardiac Parameters pre and post RT Citation Format: Faheem Farooq, Dillon Cason, Nisha Ohri, Shicha Kumar, Allison Grann, Anna Litvak, Shridar Ganesan, Bruce G. Haffty, Deborah Toppmeyer, Coral Omene, Mridula A. George. Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-08.

Abstract P1-10-18: Impact of Adjuvant Chemoradiation on cardiopulmonary function and Quality of Life in Breast Cancer

Abstract Aims and Objectives – To evaluate the safety of adjuvant chemo-radiation (CTRT) for breast cancer. We report the cardio-pulmonary safety and quality of life outcome of this regimen. Methods – Stage II-III invasive breast cancer patients planned for adjuvant taxane-based chemotherapy and adjuvant radiotherapy (RT) between April 2019 to December 2020 were eligible irrespective of prior neo-adjuvant therapy. Patients received standard 3D conformal radiotherapy (40 Gy in 15 fractions over 3 weeks ± boost for breast conservation) along with the third cycle of adjuvant taxanes in a 3- weekly schedule or the eighth cycle in a weekly schedule. Troponin T, echo cardiography and pulmonary function test were done pre-RT and repeated at 6 months from RT conclusion while quality of life was evaluated pre-RT, at RT conclusion and after 6 months using EORTC QLQ C30 and BR23. Results – Sixty patients were analysed. The median ejection fraction pre and post CTRT was 60% (p=0.177). The median value of Troponin T at baseline was 37 which decreased to 20 post CTRT (p=0.009). Of the 54 patients who underwent the PFT, the functional vital capacity (FCV) was 2.29 litres at baseline which was 2.2 litres post CTRT (p=0.375). No significant difference was seen for forced expiratory volume (FEV) at 1 second (1.86 vs. 1.82: p=0.365), FEV1/FVC (81.5 vs. 81.43; p=0.9) and diffusing capacity for carbon monoxide (DLCO) (88.3 vs. 87.6; p=0.62) at baseline and post CTRT respectively. There was a significant improvement in QOL scores for nausea, vomiting, pain, constipation, loss of appetite and hair loss post RT 6 months. Conclusion- Patients treated with taxane-based adjuvant CTRT had stable cardio-pulmonary profile at 6 months compared to pre-RT. Quality of life scores improved after treatment for most of the domains compared to the pre-RT scores. Table 1. Calculated scores of EORTC QLQ-C30 and BR23 scales for breast cancer patients at baseline, post CTRT and at first follow up of six months. Citation Format: AKANKSHA ANUP, Tabassum Wadasadawala, CARLTON JOHNNY, RAJIV SARIN, RIMA PATHAK, REVATHY KRISHNAMURTHY, Sudeep Gupta, VANI PARMAR, Jaya Ghosh, JYOTI BAJPAI, SEEMA GULIA. Impact of Adjuvant Chemoradiation on cardiopulmonary function and Quality of Life in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-18.

Novel imino-thiazoloquinoxaline derivatives against renal cell carcinoma: less radiation-damaging approach

Renal cell carcinoma (RCC) is the most fatal tumor in the urinary system. Resistance development and unmet effective responses, request new anticancer agents with better therapeutic index. Ten new imino-thiazolo-quinoxaline derivatives (5a-j) were synthesized and preliminary evaluated for downregulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) activity taking sorafenib as a reference drug. Compounds 5d & 5h showed potent inhibition to VEGFR-2 activity at IC50 89.35 nM & 60.64 nM, respectively, then they both were further evaluated in-vitro against urinary bladder cancer cell line T-24 taking sorafenib as a reference drug. Compound 5h displayed nearly anticancer activity to sorafenib against T-24 cell line in all concentrations tested except at concentration 10 µM where it highly suppressed cell viability to 6.71 % compared to 15.15% of sorafenib. Compound 5h was then evaluated for its ameliorative efect against radiation induced renal tissue injury. Assessment of pro-angiogenic (VEGFR-2), pro-fibrotic (transforming growth factor-beta 1 (TGF-β1)) and apoptotic (caspase-3) markers, as well as histopathological examinations were performed on kidney of irradiated mice. Results showed ability of compound 5h to downregulate VEGFR-2 activity and its cytotoxic effect against RCC, in addition to mitigation of radiation induced renal tissue injury. Ethyl imino-thiazoloquinoxaline carboxylate derivative 5h showed a potential cytotoxic activity against RCC and could be considered a promosing alleviative candidate when employed post radiotherapy regimen.Graphical

Determinants of Keloid recurrence: The Nairobi keloid recurrence scoring system; A cohort, prospective study

BackgroundKeloid disease is a fibro-proliferative disorder characterized by excessive deposition of collagen. Keloids has shown high recurrence rate. We undertook this study to determine what factors influence recurrence of the disease with the aim of developing a keloid recurrence scoring system. MethodsThis was a cohort prospective longitudinal study of patients who presented with keloids, managed by surgical excision followed by post excision radiotherapy. Post-surgery patients were followed up for at least two years to determine recurrence. Variables analyzed included patients’ history, clinical presentation and keloid histology. Data captured were analyzed using SPSS version 21. Student T-test and Chi-square test were used to compare means and frequencies respectively at 95% confidence level (P-Value <0.05). Multi regression analysis was done to determine the contributions of various variables to keloid recurrence. ResultsNinety patients were followed up in the study for duration of two years. Overall keloid recurrence was 21% with male patients having a significantly higher recurrence rate of 31% compared to the female at 12%. The recurrence rates were also higher in familial keloids at 27.7% compared to sporadic keloids at 18.5%. Other factors that influenced recurrence included anatomical location, patient's blood group and histological composition of the keloid. Multiple regression analysis done demonstrated that gender and family history was the biggest contributor to keloid recurrence. ConclusionKeloid recurrence is influenced by many factors including family history, clinical presentation and keloid histology. A Keloid recurrence scoring system encompassing these factors could assist in the determination of post excision management as well as prediction of the likelihood of recurrence.

Function Preservation in Head and Neck Cancers

The treatment of head and neck cancers can have a significant impact on function and appearance, which results in impairment of quality of life. Various long-term sequelae of treatment include speech and swallowing difficulty, oral incompetence, trismus, xerostomia, dental caries and osteoradionecrosis. Management has evolved from single modality treatment of either surgery or radiation to multimodality treatment to attain acceptable functional outcomes. Brachytherapy, also known as interventional radiotherapy, with its ability to deliver high doses centrally to the target, has been shown to improve local control rates. Due to the rapid fall-off of the dose of brachytherapy there is better organ at risk sparing as compared with that of external beam radiotherapy. In the head and neck region, brachytherapy has been practiced in various sites, including the oral cavity, oropharynx, nasopharynx, nasal vestibule and paranasal sinuses. Additionally, brachytherapy has also been considered for reirradiation as a salvage. Brachytherapy can also be considered as a perioperative technique together with surgery. Close multidisciplinary cooperation is required for a successful brachytherapy programme. In oral cavity cancers, depending on the location of the tumour, brachytherapy has been shown to preserve oral competence, maintain tongue mobility, maintain speech, swallowing and the hard palate. Brachytherapy in oropharyngeal cancers has been shown to reduce xerostomia and also reduce dysphagia and aspiration post-radiation therapy. For the nasopharynx, paranasal sinus and nasal vestibule, brachytherapy preserves the respiratory function of the mucosa. Despite such an incomparable impact on function and organ preservation, brachytherapy is an underutilised technique for head and neck cancers. There is a strong need to improve brachytherapy utilisation in head and neck cancers.