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Post mastectomy radiotherapy for elderly patients with intermediate risk (T1-2N1 OR T3N0) breast cancer: a systematic review and meta-analysis

Tseng M, Vellayappan B, Choong R, Appalanaido GK, Soon YY

Transl Cancer Res, 2020 Jan;9(Suppl 1):S23-S28.
PMID: 35117945 DOI: 10.21037/tcr.2019.07.23

Background: To determine if PMRT for elderly patients (>65 years old) with intermediate risk breast cancer (T1-2N1, T3N0) improves outcomes.
Methods: We performed a systematic review and meta-analysis to compare the effects of PMRT to no PMRT for elderly patients with intermediate-risk breast cancer. We searched PubMed for eligible studies from Jan 2008 to Dec 2018. We assessed the methodological quality of the included studies using the ROBINS-I tool and performed the meta-analysis with random effects model. The primary outcome of interest was overall survival (OS); secondary outcomes were breast cancer specific survival (BCSS), loco-regional (LRR) and distant disease recurrence (DDR).
Results: We found 2 retrospective cohort studies with 743 patients directly comparing PMRT to no PMRT. Both studies were judged to have serious risk of bias in their methodological quality. The pooled results suggest that PMRT was associated with a 20% relative reduction in the hazard in death, ranging from 41% relative reduction, a substantial negative association to 10% relative increase, a small positive association (HR 0.80, 95% CI: 0.59-1.1, P=0.62, I2=0%). PMRT was also associated with a 17% relative reduction in the hazard for breast cancer related death, ranging from 52% relative reduction, a substantial negative association to 41% relative increase, a substantial positive association (HR 0.83, 95% CI: 0.48-1.41, P=0.48, I2=0%). One study did not observe any significant differences in LRR and DDR between the two groups.
Conclusions: The survival benefits from PMRT in unselected elderly patients with intermediate risk breast cancer is unclear. Further research to better select elderly patients who may benefit from PMRT is warranted. Patients with a multiple pathological risk factors suggestive of high risk of loco-regional recurrence post-mastectomy should consider PMRT.
Fulltext Brachytherapy of tongue carcinoma in a patient with difficult airway: anesthetic considerations

Ghaffar ZA, Chong SE, Tan KL, Appalanaido GK, Musa MY, Hussin HB, et al.

J Contemp Brachytherapy, 2018 Dec;10(6):573-576.
PMID: 30662482 DOI: 10.5114/jcb.2018.79856

The practice of brachytherapy in unresectable tongue carcinoma is gaining popularity. However, this procedure poses specific anesthetic challenges, particularly challenges of airway sharing and a higher rate of difficult airway. We report a 74-year-old chronic smoker, chronic alcoholic with history of stroke, who had undergone brachytherapy for tongue carcinoma. Apart from a huge tongue tumor, he had an epiglottic mass but refused elective tracheostomy. This had led to a few critical states throughout the process of treatment, including a metabolic crisis due to thiamine deficiency and difficult airway crisis. To our best knowledge, there have been no reported case on a patient with vocal cord mass undergoing tongue brachytherapy. We hope sharing of this experience may aid the management of similar patients in future.
Fulltext Case Report-Staged brachytherapy achieving complete metabolic response in unresectable oligometastatic colorectal cancer to the liver

Appalanaido GK, Bahajjaj SIBZ, Shukor SA, Ahmad MZ, Francis HCH

Oxf Med Case Reports, 2021 Apr;2021(4):omab016.
PMID: 33948189 DOI: 10.1093/omcr/omab016

Liver is the most common site for metastasis from colorectal cancer (CRC). Non-surgical treatment options for oligometastatic CRC confined to the liver which represents an intermediate state in the metastatic cascade are fast expanding. Currently, several liver-directed local therapeutic options are available, such as hepatic arterial infusion (HAI) therapy, radio-frequency ablation (RFA), transarterial chemoembolization (TACE), stereotactic body radiotherapy and high dose rate brachytherapy (HDRBT). Many factors such as patient's fitness, liver function (LF), tumour size, location of the tumour in the liver and scheduling of systemic therapy need to be considered when selecting patients for surgery or local liver-directed therapy. This case report illustrates a successful local treatment with staged HDRBT for a large and unresectable, liver only oligometastatic disease from CRC. This patient underwent 4 cycles of chemotherapy (FOLFOX 4) followed by primary tumour resection and first stage of HDRBT to liver for a residual 14 cm tumour after the chemotherapy. After completing a further 4 cycles of chemotherapy with the same regimen, the tumour remained stable at 8 cm. She underwent a second stage of HDRBT to the same lesion and a repeat PET-CT scan done 8 weeks after the second HDRBT showed complete metabolic response. To our knowledge, this is the largest CRC metastatic liver lesion that has been successfully treated with HDRB.
Diagnosis of cancer is not a death sentence: Examining posttraumatic growth and its associated factors in cancer patients

Leong Abdullah MFI, Hami R, Appalanaido GK, Azman N, Mohd Shariff N, Md Sharif SS

J Psychosoc Oncol, 2019 03 01;37(5):636-651.
PMID: 30821660 DOI: 10.1080/07347332.2019.1574946

Objectives: Posttraumatic growth (PTG) is the experience of positive psychological growth as a result of struggle with highly challenging life crises. This study was conducted to investigate the degree of PTG and its associated factors, as well as to identify which positive psychological parameters most significantly associated with greater PTG among Malaysian cancer patients. Design, sample, & methods: This cross-sectional survey included 195 patients with different cancer diagnoses. Perceived spousal support, level of hope, level of optimism, and PTG were measured using various validated indexes. Findings: The total mean score for PTG Inventory-Short Form (PTGI-SF) was 39.87 (±9.09). Female gender, Islamic religious belief, and having higher level of hope and greater spousal support were associated with a higher PTGI-SF score, and the most significant predictor was the hope scale. Conclusions: Malaysian cancer patients exhibited a high level of PTG, and hope was the positive psychological factor which was most significantly associated with PTG. Implications for psychosocial providers: Psychosocial interventions that promote positive psychology should be included in the treatment for cancer patients.
Lateral wedge with medial only cardiac shielding (LEMONADE) technique in left chest wall adjuvant radiotherapy

Abdullah R, Appalanaido GK, Shukor SA, Zin HM, Abd Aziz MZ, Ishak N

Rep Pract Oncol Radiother, 2021;26(6):892-898.
PMID: 34992860 DOI: 10.5603/RPOR.a2021.0105

Background: This dosimetric study compared lateral wedge with medial only cardiac shielding (LEMONADE) technique, for left chest wall (LCW) irradiation against three other commonly used techniques.
Materials and methods: Dosimetric parameters of 22 consecutive LBC patients treated using the P1 (LEMONADE technique) were compared with 3 other virtually reconstructed plans : no cardiac shielding with paired wedges; P2 (paired wedges and medial only Y-direction shielding) and P3 (paired wedges and bilateral Y-direction shielding).
Results: P1 showed better target volume (TV) coverage with the mean 90% isodose coverage of 85.59% ± 5.44 compared to 78.90% ± 8.59 and 74.22% ± 9.50 for P2 and P3, respectively. Compared to no cardiac shielding, for a 4.65% drop in TV coverage the V26Gy of heart dropped from 6.68% to a negligible 0.85% for P1. TV receiving < 30Gy is also significantly lesser for P1 compared to P2 and P3 (5.42% vs 10.64% and 15.8%), whilst there is a small difference of 2.75% between no cardiac shielding and P1.
Conclusion: With the improvement in BC survival rate, cardiac toxicity associated with adjuvant irradiation for LBC is a major concern. P1 (LEMONADE) technique has a good compromise between cardiac sparing and target coverage and should suffice for most LCW irradiations. Furthermore, the LEMONADE technique is a simple, reproducible and involves fast planning for cardiac sparing, which is ideal for under-resourced departments with heavy workload.
Fulltext Re-irradiation Using Stereotactic Radiotherapy: A Bibliometric Analysis of Research Trends

Mohamed Yoosuf AB, Ajmal Khan M, Abdul Aziz MZ, Mansor S, Appalanaido GK, Alshehri S, et al.

Cureus, 2023 May;15(5):e39600.
PMID: 37384098 DOI: 10.7759/cureus.39600

The objective of this research is to conduct a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) to examine the current research topics and trends pertaining to stereotactic-based re-irradiation. A bibliometric search was conducted for re-irradiation-related literature published in English from the WoSCC database from 1991 to 2022, using VOSviewer to visualize the results. The extracted information comprises the publication year, overall citation count, average citation rate, keywords, and research domains. We conducted a literature review to identify trends in research on re-irradiation. A total of 19,891 citations were found in 924 qualifying papers that came from 48 different nations. The number of publications and citations has grown steadily since 2008 with the highest number of publications in the year 2018. Similarly, a substantial increase in the number of citations has increased since 2004 and the citation growth rate has been positive between 2004 and 2019 with a peak in 2013. The top authorship patterns were six authors (111 publications and 2498 citations), whereas the highest number of citations per publication was attained with an authorship pattern of 17 authors (C/P = 41.1). The collaboration patterns analysis showed that the largest proportion of publications emanated from the United States with 363 publications (30.9%), followed by Germany with 102 publications (8.7%), and France with 92 publications (7.8%). The majority of the analyzed studies were focused on the brain (30%), head and neck (13%), lung (12%), and spine (10%) and there have been emerging studies on the use of re-irradiation for lung, prostate, pelvic and liver utilizing stereotactic radiotherapy. The main areas of interest have changed over time and are now based on a multidisciplinary approach that integrates advanced imaging techniques, stereotactic treatment delivery, the toxicity of organs at risk, quality of life, and treatment outcomes.
Fulltext Accuracy of a time-of-flight (ToF) imaging system for monitoring deep-inspiration breath-hold radiotherapy (DIBH-RT) for left breast cancer patients

Abubakar A, Shaukat SI, Karim NKA, Kassim MZ, Lim SY, Appalanaido GK, et al.

Phys Eng Sci Med, 2023 Mar;46(1):339-352.
PMID: 36847965 DOI: 10.1007/s13246-023-01227-6

Deep inspiration breath-hold radiotherapy (DIBH-RT) reduces cardiac dose by over 50%. However, poor breath-hold reproducibility could result in target miss which compromises the treatment success. This study aimed to benchmark the accuracy of a Time-of-Flight (ToF) imaging system for monitoring breath-hold during DIBH-RT. The accuracy of an Argos P330 3D ToF camera (Bluetechnix, Austria) was evaluated for patient setup verification and intra-fraction monitoring among 13 DIBH-RT left breast cancer patients. The ToF imaging was performed simultaneously with in-room cone beam computed tomography (CBCT) and electronic portal imaging device (EPID) imaging systems during patient setup and treatment delivery, respectively. Patient surface depths (PSD) during setup were extracted from the ToF and the CBCT images during free breathing and DIBH using MATLAB (MathWorks, Natick, MA) and the chest surface displacement were compared. The mean difference ± standard deviation, correlation coefficient, and limit of agreement between the CBCT and ToF were 2.88 ± 5.89 mm, 0.92, and - 7.36, 1.60 mm, respectively. The breath-hold stability and reproducibility were estimated using the central lung depth extracted from the EPID images during treatment and compared with the PSD from the ToF. The average correlation between ToF and EPID was - 0.84. The average intra-field reproducibility for all the fields was within 2.70 mm. The average intra-fraction reproducibility and stability were 3.74 mm, and 0.80 mm, respectively. The study demonstrated the feasibility of using ToF camera for monitoring breath-hold during DIBH-RT and shows good breath-hold reproducibility and stability during the treatment delivery.
Effectiveness of Robotic Stereotactic Radiotherapy in Patients Undergoing Re-irradiation: A Review

Mohamed Yoosuf AB, Alshehri S, Abdul Aziz MZ, Mansor S, Appalanaido GK, Alqathami M

Cureus, 2023 Aug;15(8):e43500.
PMID: 37719625 DOI: 10.7759/cureus.43500

Stereotactic ablative radiotherapy (SABR) is a possible treatment option for patients who develop recurrence within or at the edge of a previously irradiated volume. Robotic stereotactic radiotherapy is the result of technological advances in robotic precision, real-time imaging, non-invasive, highly customizable treatment plan, and delivery with sub-millimeter accuracy. This article reviews the radiobiologic, technical, and clinical aspects of robotic-based SABR re-irradiation for various anatomical sites. An extensive literature search was performed to identify articles on the utilization of robotic stereotactic radiotherapy for patients undergoing re-irradiation. The reported prescription dose and fractionation data along with outcomes such as overall survival, local control rates, and toxicities were qualitatively reviewed. The findings consistently indicate that re-irradiation using robotic SABR provides encouraging survival rates with minimal toxicity in the clinical setting of various anatomical sites delivered using locally non-invasive means where other treatment options are scarce.
Fulltext Palliative brachytherapy to axilla and hypopharynx in elderly patient with hypopharyngeal squamous cell carcinoma - case report

Appalanaido GK, Shukor SA, Fan AS, Chong SE, Hussin H, Karim NKA, et al.

Rep Pract Oncol Radiother, 2021;26(4):647-653.
PMID: 34434581 DOI: 10.5603/RPOR.a2021.0076

Brachytherapy (BT) is an important local treatment of tumor and it can be applied to different anatomical sites either in a curative or palliative setting. BT can deliver large dose of radiation to the tumor while sparing the surrounding normal tissue which translates into a better therapeutic ratio compared to external beam radiotherapy. However, the evidence for the use of brachytherapy in the palliative setting is lacking in the literature. In this case report, we describe the brachytherapy technique and outcome of a patient with squamous cell carcinoma of the hypopharynx who underwent palliative brachytherapy to the hypopharynx and metastatic tumor at the right axilla.
Fulltext Older Cancer Patients during the COVID-19 Epidemic: Practice Proposal of the International Geriatric Radiotherapy Group

Nguyen NP, Vinh-Hung V, Baumert B, Zamagni A, Arenas M, Motta M, et al.

Cancers (Basel), 2020 May 19;12(5).
PMID: 32438703 DOI: 10.3390/cancers12051287

The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.
Fulltext Whole-lung Low Dose Irradiation for SARS-Cov2 Induced Pneumonia in the Geriatric Population: An Old Effective Treatment for a New Disease? Recommendation of the International Geriatric Radiotherapy Group

Lara PC, Nguyen NP, Macias-Verde D, Burgos-Burgos J, Arenas M, Zamagni A, et al.

Aging Dis, 2020 May;11(3):489-493.
PMID: 32489696 DOI: 10.14336/AD.2020.0506

A cytokine storm induced by SARS-Cov2 may produce pneumonitis which may be fatal for older patients with underlying lung disease. Hyper-elevation of Interleukin1 (IL-1), Tumor necrosis factor-1alfa (TNF-1 alfa), and Interleukin 6 (IL-6) produced by inflammatory macrophage M1 may damage the lung alveoli leading to severe pneumonitis, decreased oxygenation, and potential death despite artificial ventilation. Older patients may not be suitable candidates for pharmaceutical intervention targeting IL-1/6 blockade or artificial ventilation. Low dose total lung (LDTL) irradiation at a single dose of 50 cGy may stop this cytokine cascade, thus preventing, and/or reversing normal organs damage. This therapy has been proven in the past to be effective against pneumonitis of diverse etiology and could be used to prevent death of older infected patients. Thus, LDRT radiotherapy may be a cost-effective treatment for this frail patient population whom radiation -induced malignancy is not a concern because of their advanced age. This hypothesis should be tested in future prospective trials.
Fulltext Immunotherapy and Radiotherapy for Older Cancer Patients during the COVID-19 Era: Proposed Paradigm by the International Geriatric Radiotherapy Group

Nguyen NP, Baumert BG, Oboite E, Motta M, Appalanaido GK, Arenas M, et al.

Gerontology, 2021;67(4):379-385.
PMID: 33784693 DOI: 10.1159/000514451

BACKGROUND: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus.
SUMMARY: Immunotherapy has less effect on the patient bone marrow compared to chemotherapy. The potential synergy between radiotherapy and immunotherapy may improve local control and survival for older patients with selected cancer. Preliminary data are encouraging because of better survival and local control in diseases which are traditionally resistant to radiotherapy and chemotherapy such as melanoma and renal cell carcinoma. Key Message: We propose a new paradigm combining immunotherapy at a reduced dose and/or extended dosing intervals and hypofractionated radiotherapy for older patients with selected cancer which needs to be tested in future clinical trials.

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