Radiation oncology in times of COVID-2019: A review article for those in the eye of the storm – An Indian perspective

Abstract

The global COVID-2019 pandemic has presented to the field of radiation oncology a management dilemma in providing evidence-based treatments to all cancer patients. There is a need for appropriate measures to be taken to reduce infectious spread between the medical healthcare providers and the patient population. Such times warrant resource prioritization and to continue treatment with best available evidence, thereby reducing the risk of COVID-2019 transmission in times where the workforce is reduced. There has been literature presented in different aspects related to providing safety measures, running of a radiation department and for the management of various cancer subsites. In this article, we present a comprehensive review for sustaining a radiation oncology department in times of the COVID-2019 pandemic.

Radiotherapy based management during Covid-19 pandemic – A systematic review of presented consensus and guidelines

“…in poor PS) Anaplastic oligodendroglioma (up to 4-6 month) Continue any progressing RT: High priority: Large benign tumors with acute symptoms (pressure, loss of sight); posterior fossa tumors (malignant or non-malignant) causing life-threatening hydrocephalus. High-intermediate priority: Medulloblastoma; Young Grade 3 glioma Intermediate priority: High-grade glioma in young fit patients Low priority: Small benign tumors; HGG in elderly, low-grade glioma ( Neuro-oncology treatment guidance during COVID-19 pandemic, 2021 ) High-Grade Glioma: Standard of care (surgical resection followed by RT) Considerable tumor volume (gliomatosis) Involvement of brainstem/spinal cord Grade III astrocytoma Delicate or older patients: Hypo-F accelerated course (34 Gy /10 frs or 40.05 Gy / 15 frs and 25 Gy / 5 frs for smaller tumors) IDH-wild-type and IDH-mutant glioma: shorten RT courses ( Vordermark, 2020a ) Low-grade glioma asymptomatic meningioma G1-2 Glioblastoma, Frail/elderly (40 Gy / 15 frs or 25 Gy / 5 frs) ( Kochbati et al, 2020 ) GBM: - Aged ≥ 65 yrs with excellent PS: Hypo-F RT (40 Gy /15 frs) - Aged < 65 yrs with good PS (KPS ≥ 70): standard fractionation (60 Gy / 30 frs) -Poor PS (KPS < 50): palliative regimens (34 Gy /10 frs or 25 Gy /5 frs) ( Noticewala et al, 2020b ) GBM: Elderly with poor KPS/unmethylated - Grade 1, Grade 2, and Grade 3 meningiomas - Schwannomas - Low-grade gliomas - Meningioma: (Hypo-F RT) Grade 1, Grade 2: 25 Gy / 5 frs Grade 3: 45 Gy in 15 fractions -Schwannomas: frameless SRS/ Hypo-F RT (25 Gy / 5 frs) -GBM: Elderly with poor KPS/methylated: 34 Gy /10 frs or 5 Gy weekly × 6 weeks Younger patients good KPS: Hypo-F RT (60 Gy / 20 frs (SIB technique) -Medulloblastoma: Start with posterior fossa boost and then switch over to craniospinal RT with VMAT/IMRT -Cystic craniopharyngiomas: For all post-op patients, start on RT ( Balakrishnan et al, 2020 ) Asymptomatic meningioma grade I-II Asymptomatic AVM Grade 3 glioma (anaplastic oligodendroglioma) for 4-6 months Non-co-deleted (anaplastic astrocytoma) Hypo-F RT: 40 Gy/15 frs or 30 Gy/6 frs ( Hinduja et al, 2020 ) …”

“… Postpone RT up to 20 weeks after the completion of surgical or systemic treatment: -Tumor T1, T2, N0 hormone-sensitive, HER2, > 40 yrs, patients on hormone therapy, unfavorable prognostic factors (close margins, G3) -Begin RT up to 8 weeks after the completion of surgical or systemic treatment: Inflammatory breast cancer, massive metastases to ≥4 lymph nodes, massive LVI, TNBC with N+, yp N+, and regional recurrence. -Begin RT up to 16 weeks after the completion of surgical or systemic treatment: T4, TNBC, N0, yp T + and N0, LVI (NOS), Invasive cancer in patients < 40 yrs, ER + with 1–3 N + and other unfavorable prognostic factors (G3, LVI) ( Łacko et al, 2020 ) Good risk DCIS: Low/intermediate grade, < 2.5 cm, margin >3 mm EBC: -Age >70 yrs, post BCS - T1, N0, ER+, margins clear -Age >65yrs, ER+, N0, T1/T2 (up to 3 cm), clear margins; grade 3 or LVI Boost dose for DCIS / EBC (>60 yrs) DCIS: up to 12 weeks EBC post BCS: delay RT without chemotherapy up to 20 weeks Good risk DCIS: ER/PR+, EBC/DCIS ER + disease with N1a nodes (1-3 nodes)/ Node negative TNBC/Pathological N0 post-NACT / LVI EBC: Young premenopausal women Locally advanced breast cancer Boost dose for EBC: - Hypo-F RT -SIB or concomitant boost (daily or weekly) -5.2 Gy single fraction after ultra- Hypo-F RT Inflammatory breast cancer/Residual nodal disease after NACT/N2 disease (4 or more nodes)/Recurrent disease/Node positive TNBC/Extensive LVI ( Hinduja et al, 2020 ) Adjuvant RT (DCIS): low-risk cases (age ≥ 50 yrs with no necrosis, low grade, small tumor size, at least 2 mm margins) Invasive breast cancers (node-negative): post-op, patients aged ≥ 65 yrs with HR + tumors Adjuvant RT (DCIS): higher-risk cases (Hypo-F RT) -APBI:40 Gy/10rs, 38.5 Gy/10 frs twice a day over 5–8 days -FAST FORWARD regimen for WBI: 26 Gy / 5 daily frs Node negative invasive cancer: -Low-risk patients aged 40–64 yrs (maximum tumor size 3 cm, ER+) APBI: 30 Gy / 5 frs daily (IMRT) or 40 Gy / 10 frs daily (3D CRT) WBI: 40 Gy / 15 frs (standard Hypo-F or FAST FORWARD regimen) During DORSCON Red: APBI using 30 Gy / 5 frs or WBI using 26 Gy / 5 frs Other patients (age ≤40 yrs; or high-risk, age > 40 years; or tumors > 3 cm, high grade, ER-, HER2+ or involved margin), WBI or PMRT for tumors > 5 cm or positive margin): -Standard Hypo-F RT 40 Gy/15 frs or the FAST FORWARD regimen If the boost is indicated: simultaneously (48 Gy /15 frs or sequentially as 10.5 Gy/3 frs During DORSCON Red: WBI or PMRT using 26 Gy / 5 frs Node positive invasive cancer: - N1 disease: adjuvant RT to the breast/chest wall and ipsilateral supraclavicular fossa (and axilla) using standard Hypo-F RT 40 Gy / 15 frs or 26 Gy / 5 frs - Adjuvant RT to IMNC with N2 disease using standard Hypo-F RT 40 Gy /15 frs Boost: simultaneously using 48 Gy / 15 frs or sequentially 10.5 Gy /3 frs During DORSCON Red: adjuvant RT using 26 Gy /5 frs ( Chan et al...…”

“… SCLC: - CRT for limited-stage - Palliative or ablative radiotherapy (SBRT) ( Omeroglu Simsek, 2020 ) Postpone initiation of treatment by 4 weeks: -Post-Operative Radiotherapy (PORT) NSCLC - Prophylactic Cranial Irradiation (PCI) SCLC Use less treatment sessions: - SABR as possible. - Hypo-F RT regimens ( Bakhribah et al, 2020 ) Extensive-stage SCLC: PCI - Stage I NSCLC: 45 - 54 Gy /3 frs or 48 - 50 Gy / 4 or 5 frs or 30 - 34 Gy /1 fr in select patients (SBRT/ablation) - Locally advanced NSCLC (stage III): 60 Gy / 24 frs or 55 Gy / 20 frs or up to 60 Gy / 15 frs (Hypo-F RT schedule) - Limited-stage SCLC: twice-per-day RT (cCRT) PCI for age < 75 yrs ( Singh et al, 2020 ) Extensive SCLC (PCI or palliative intent) Locally advanced (palliative): - 40 Gy / 15 frs - 39 Gy / 13 frs - 16 Gy / 2 frs ( Kochbati et al, 2020 ) SCLC, Extensive: - PCI - Consolidation thoracic RT in extensive-stage disease Stage I-IIIB tumor operated: Short delay in RT if R0 resection NSCLC, T1/2N0M0, medically inoperable; peripheral: -SBRT 30-34 Gy/single fr (T1 N0M0) -54 Gy / 3 frs in 1.5 weeks (Eligibility includes T1, 2 (<5 cm), T3 < 5 cm, chest wall involvement positive, no mediastinal or bronchial tree invasion) -48 Gy / 4 frs daily RT NSCL, T1/2N0M0, medically inoperable, central: - 60 Gy / 8 daily frs -70 Gy / 10 daily frs -50 Gy / 5 daily frs Stage III, Locally advanced NSCLC: -55 Gy / 20 frs with concurrent /sequential chemotherapy -60 Gy /15-20 frs NSCLC, advanced- inoperable, large for Palliative RT: 8 - 10 Gy/1-2 frs SCLC, localized: 40-42 Gy /15 daily frs ( Hinduja et al, 2020 ) Curative treatment for stage III NSCLC: Hypo-F in cCRT strategy (60–66 Gy / 22–30 frs and 50 Gy / 20 frs) Inoperable stage II-III NSCLC Limited stage SCLC Palliative NSCLC (spinal cord compression or SVCO) Early-stage NSCLC: SABR:30–34 Gy /1 fr to 48–54 Gy / 3 frs Central tumors: Hypo-F RT (50–60 Gy /15 frs) Inoperable early-stage NSCLC and operable NSCLC: SBRT Stage II NSCLC: definitive RT ( Stepanović and Nikitović, 2020 ) Adjuvant RT (pathological N2 or R1 post-op): after chemotherapy or 3 months after surgery Early-stage disease: SBRT for tumors <2.0 cm (a single fraction of 30 − 34 Gy) Adjuvant...…”

“… Total body irradiation, retinoblastoma, nasopharynx, and head and neck malignancies ( Hinduja et al, 2020 ) Considering Hypo-F where RT is required: Wilms tumor Low-grade glioma Palliative cases with urgent symptoms ( Sullivan et al, 2020 ) Individualize interruption for a suspected or confirmed case of COVID-19 Pediatric tumors: No changes and no delay of RT ( Carvalho et al, 2020 ) Lymphoma and hematological malignancies Consolidation therapy for high-grade lymphomas Low-grade lymphomas (most patient) High-grade lymphomas with severe or life-threatening symptoms ( Wright et al, 2020 ) HL: if RT not available Peripheral T-Cell Lymphomas (PTCL): aggressive disease ( Perini, 2020 ) Early-stage HL (RT elimination costs of 6–8% disease control) ( Vordermark, 2020a ) For ≥ 60 yrs: - for the palliative purpose where alternative treatment is available - for localized low-grade lymphomas if completely excised - for localized nodular lymphocyte-predominant HL if completely excised - in consolidation RT for diffuse large B-cell lymphoma/ aggressive NHL for those who have completed a full chemotherapy course with complete remission. When there is no/little expected adverse effect: - for asymptomatic localized low-grade lymphomas; - for localized nodular lymphocyte-predominant HL - in a palliative setting for low-grade lymphomas in stable cases; - for whom develop COVID-19 infection before commencing RT Using alternative Hypo-F RT when RT cannot be omitted or delayed to maintain high cure/palliation rates without excessive toxicity (e.g., For patients with symptomatic sites of disease and Localized aggressive NHL, primary RT alone, and NK-/T-cell lymphoma) ( Yahalom et al, 2020 ; Di Ciaccio et al, 2020 ) In a minority of cases, if alternative treatment options were available Shortening of treatment via Hypo-F RT or limitation of total dose for hemato-oncological patients: - Painful osteolytic lesion caused by multiple myeloma in non-weight bearing bones after stabilizing surgery: 8 Gy/1 fr, 20 Gy/5frs, 24 Gy/8frs, and 30 Gy/10frs - Osteolytic lesion of multiple myeloma in weight-bearing bones (e.g., axial skeleton) without surgery: 20 Gy...…”

“… Adding approx. 5 Gy per week for each week of BT delay beyond seven weeks, respecting (OARs) tolerance doses ( Barthwal et al, 2020 ) - Reducing the number of applications by delivering multiple fractions with each application - Using higher dose/fr (fewer fraction number) considering the indications (e.g., 3 × 8 Gy or 4 × 7 Gy) ( Miriyala and Mahantshetty, 2020 ; ElMajjaoui et al, 2020 ; Kumar and Dey, 2020 ; Ismaili and Elmajjaoui, 2020 ) Adjuvant treatment: 9 Gy / 2 frs over 2 weeks, over conventional 7 Gy / 3–4 frs or 6 Gy / 5 frs ( Upadhyay and Shankar, 2020 ) 9 Gy × 2 frs weekly (in patients with low volume disease post-RT and in whom inferior local control) ( Kumar and Dey, 2020 ) Stages IB3, IIA2-IIIC2, and early IVA: Intracavitary HDR brachytherapy 3 frs Stages IA1, IA2, IB1, IB2, IIA1: Vault brachytherapy 12 Gy/2 frs ( Hinduja et al, 2020 ) For centers with single brachytherapy operating: postpone at least 24 days or until the infection is resolved Reduced number of fractions: 24 Gy/3 frs or 28 Gy/4 frs HDR ICBT: 7 Gy/4 frs at 1 week apart or 2 frs per day separated by a 6 h interval For patients >70 yrs, significant comorbidities, small tumors, or responding well to RT: -Shortened schedule (9 Gy /2 frs at 1 week apart) -Brachytherapy for cervical cancer (stage IB1, IIIB) ( ElMajjaoui et al, 2020 ) Advanced cervical cancer: temporarily defer interstitial brachytherapy ( Kwek et al, 2021 ) Uterine - Postpone BT but no more than 12 weeks after surgery ( Williams et al, 2020 ) Endometrial - Standard treatment (preferably three frs) ( Aghili et al, 0 ) Inoperable definitive positive COVID-19 symptomatic patients: - Hold on RT for 10-14 days - Start BT after recovery ( …”