Table 2.

Summary of international guidelines or national multi-cancer recommendation for brachytherapy prioritization during COVID-19 pandemic.

Cancer type		Hold BT and choose another treatment option	Delay BT until the end of the pandemic	Continue BT during the pandemic
CNS		Brain (For primary or metastases/adjuvant cases):
		- Avoid BT until pandemic solves
		- SRS/SRT for glioma or metastatic cases (Mohindra et al., 2020)
Head and neck				Oral tongue (pT1-T2, N0) high risk of local recurrence:
				- Adjuvant BT (39 Gy /fr in 7 days, twice daily instead of 60 Gy /30 frs by EBRT) (Aghili et al., 0)
		Definitive/boost oral cavity/oropharynx, boost nasopharynx or any re-irradiation:
		- Avoid BT until pandemic solves
		- For COVID-19+ patients, continue EBRT rather than BT boost (Mohindra et al., 2020)
				SSC of lip, oral mucosa, or nasal region cases: - Continue (Cyrus et al., 2020)
		Switch interstitial BT to EBRT		If BT can be employed as a sole modality for cases such as the lip and oral mucosa (Barthwal et al., 2020)
				Recurrent nasopharyngeal carcinoma: time-sparing interstitial or intracavitary brachytherapy (if feasible)
				- 198Au grains: 60 Gy
				- 125I grains: 130 Gy; 120 Gy
				- HDR intracavitary: 24 Gy / 3 frs (Svajdova et al., 2020)
Breast				Early-stage cases:
				- Use balloon- or multicatheter-based BT instead of EBRT ()
			Low-risk cases:
			Postpone interstitial BT for up to 16–20 weeks for ER + invasive cases or 12 weeks for DCIS (Mohindra et al., 2020)
			Patients prescribed for definitive or adjuvant therapy:	Early-stage:
			- Shorten BT fractionation schedules	- Neoadjuvant endocrine therapy due to delay of surgeries during the crisis;
				- Adjuvant therapy after BCS
				- Deem BT as an equivalent option to EBRT
				- BT for APBI with a single-entry intra-cavitary or multi-catheter interstitial technique after surgery
				Invasive cases:
				- Induction of therapy for within 12 weeks after surgery, not more than 20 weeks (BT after BCS) (Williams et al., 2020)
		Accelerated partial breast irradiation (Exclusive):	Accelerated partial breast irradiation (Exclusive):
		- Opt for EBRT according to local facilities (Chargari et al., 2020)	- Postpone (8–12 weeks)
		Apply EBRT instead of BT (Barthwal et al., 2020)
				Very Low-, Low- and Intermediate Risk:
				-HDR-ISBT 27 Gy/2frs Monotherapy
				- 125I LDR-ISBT
				Intermediate Risk High - Very High Risk:
				- HDR-ISBT boost 15 Gy/1 fr (Murakami et al., 2020)
Lung		For palliative and post-transplant stenosis:
		- Avoid BT until the pandemic solves (Mohindra et al., 2020)
Gastrointestinal	Esophageal			Palliation with symptoms:
				- Continue BT ()
		-Palliative and re-irradiation:
		- Avoid BT until the pandemic solves (Mohindra et al., 2020)
		BT with Endoscopic procedures (esophagus or bronchus):
		- Omit and consider EBRT options (Chargari et al., 2020)
	Hepato-biliary			Avoid delaying the treatment using BT ()
		Hilar Cholangiocarcinoma cases with COVID-19+ during RT:
		- Continue EBRT rather than BT boost
		Palliative unresectable malignant biliary obstruction or hepatocellular carcinoma cases (not for the transplant) and metastatic lesions:
		- Avert BT until pandemic solves (Mohindra et al., 2020)
	Rectal	For COVID-19+ patients:	Preoperative or definitive postpone brachytherapy until pandemic solves (Hypo-F RT) (Mohindra et al., 2020)
		- Hypo-F-EBRT rather than BT boost
				After SCRT:
				- For Unresectable, Medically inoperable, or Frail elderly cases: 10-20 Gy in 2-4 frs (Siavashpour et al., 2020)
	Anal	- Switch interstitial BT to EBRT
		- Switch to IORT if facilities are available (Barthwal et al., 2020)
Genitourinary	Prostate			Continue (Chargari et al., 2020)
				If BT can be employed as a sole modality for penile region cases (Barthwal et al., 2020)
			Low-risk patient:	High-risk patients:
			- Delay BT up to 3–6 months	- BT as a boost, avoiding any deferent:
				13·5 Gy /2 frs of BT alone or 15 Gy/1 fr as EBRT boost ()
		For COVID-19+ patients during EBRT:	High-risk cases:	High-risk cases:
		- Interrupt treatment to let recovery up to 10–14 days before restarting/plan for BT	- Delay all monotherapy BT	- Defer starting EBRT and keep on hormone therapy-- Consider EBRT boost instead of BT (Mohindra et al., 2020)
		For COVID-19+ patients after 1 st session of HDR, defer 2nd fraction to allow recovery up to10–14 days
			Low and intermediate-risk cases:	For anxious patients, minimize the time of treatment (definitive)
			- Delay BT for at least 3–6 months	Definitive or adjuvant therapy (using endocrine):
				- Shorten BT fractionation schedules (Williams et al., 2020)
			Low-risk prostate cancer (Exclusive):	Low-risk prostate cancer (Exclusive):
			- Postpone (8–12 weeks)	- Opt for surveillance
			Intermediate and high-risk prostate:	Intermediate and high-risk prostate:
			- Postpone (8–12 weeks)	- Opt for EBRT according to local facilities (Chargari et al., 2020)
		Brachytherapy should be avoided as far as possible		In centers where prostate BT is common:
				– all (HDR) monotherapy cases (2 implants) should be converted to HDR boost (single implant 15 Gy in 1 fr) or switching to EBRT or starting of ADT
				– EBRT that are due for HDR boosts (15 Gy in 1 fr) can be converted to 37.5 Gy/15 fractions,
				– For experienced centers, BT can be delivered using LDR (Barthwal et al., 2020)
			Temporarily defer certain specialized procedures (HDR-BT) (Kwek et al., 2021)
Gynecological	Cervix			locally advanced cases (excluding verified or doubtful patients with COVID-19 infection) ()
			Positive COVID-19 patients:	Negative COVID-19 patients:
			- Postpone up to 10–14 days	- Finalize treatment within 7–8 weeks (Mohindra et al., 2020)
			- Increase dose by 5 Gy / week deferent (consider OAR constraints)
			- Keep on BT boost with PPE precautions
				Chemotherapy/RT + BT ≤ 8 weeks (Williams et al., 2020)
				Boost: Continue for locally advanced case (Chargari et al., 2020)
		When that is not feasible EBRT boost should be considered.		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:	Reduced number of fractions: 24 Gy/3 frs or 28 Gy/4 frs
			postpone at least 24 days or until the infection is resolved	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) ()
			Inoperable definitive positive COVID-19 symptomatic patients:
			- Hold on RT for 10–14 days
			- Start BT after recovery (Mohindra et al., 2020)
			High-risk cases:
			- Postpone boost (8–12 weeks)
			- Opt EBRT according to local facilities (Chargari et al., 2020)
			Interstitial BT for definitive COVID-19+ cases:
			- Delay treatment up to 10–14 days after recovery
			- Increase BT dose by 5 Gy / week deferent (Mohindra et al., 2020)
			Intermediate risk endometrial cancer (Exclusive): Postpone (8–12 weeks) or opt for surveillance (Chargari et al., 2020)
		Postop vaginal cuff cases:	- Postpone BT up to 8–9 weeks after surgery
		- Avert BT boost after RT if no adverse factor exists	- Postpone BT boost by 2–3 weeks after RT (Mohindra et al., 2020)
		- COVID-19+ patients: postpone BT until pandemic solves
		Early-stage high risk	Early-stage intermediate risk:
			- Postpone BT up to 12 weeks to 6 months based on patient comorbidities
			−7 Gy (to 0.5 cm depth) in 3 frs allowing 14 days inter-fraction interval
			Stage II:
			- Postpone by 1–2 months
			- Postpone at least 24 days for COVID-19 positive cases (ElMajjaoui et al., 2020)
		Stages IA Gr I-Gr III and IB Gr I-II: Vault brachytherapy if positive margins, suboptimal surgery	Stages IB Gr 3, stage II G1 and G2 with no high-risk features, stage IIIA-IIIC: Vault brachytherapy (Hinduja et al., 2020)
		High-risk patients (received adjuvant RT): Omitting VVB	For patients with significant comorbidities: for 6 months	Patients who should start VVB: 7 Gy/3 frs (depth of 0.5 cm) with an interval spacing of 14 days between the fractions
			Intermediate-risk endometrial cancer:	Stage II endometrial cancer with poor prognostic factors (if invasion > 50 % of the myometrium, G3), and for stage I high-risk endometrial cancer: Adjuvant RT and brachytherapy (ElMajjaoui et al., 2020)
			Delaying VVB up to 12 weeks
			Stage II endometrial cancers:
			Adjuvant VVB (exclusively: if invasion < 50 % of the myometrium, G1 and 2 or after RT: if invasion > 50 % of the myometrium, G3): postpone brachytherapy by 1–2 months
			COVID-19 positive patient: postpone treatment (at least 24 days)
	Vaginal		Stage I:	Advanced stage (ElMajjaoui et al., 2020)
			- Postpone BT up to 1–6 months for patients with significant comorbidities
				Upper and lower vagina (Hinduja et al., 2020)
			Early vaginal cancer (stage I, < 5 mm of invasion) with significant comorbidities:	For advanced stage:
			postpone brachytherapy by 1–2 months	CRT followed by vaginal brachytherapy (7 Gy/3frs)
				Brachytherapy without any delay (curative treatment):
				stage I, < 5 mm of invasion, locally advanced stage (ElMajjaoui et al., 2020)
	Vulvar		low priority and only be carried out when operation theatre capacity allows it (Barthwal et al., 2020)
		Vulva: radical, adjuvant and palliative (Hinduja et al., 2020)
Sarcoma			Postpone BT boost until pandemic solves.
			For COVID-19+ patients during RT, continue EBRT rather than brachytherapy boost (Mohindra et al., 2020)
				Soft-tissue sarcoma:
				- BT alone (HDR instead of LDR with iridium-192 wires) rather than 60−66 Gy / 1·8−2 Gy/ fr adjuvant EBRT ()
Pediatrics				BT can be employed in specialized centers, especially for rhabdomyosarcoma (Barthwal et al., 2020)
		Pediatrics indication: To be discussed on an individual basis (Chargari et al., 2020)
Skin				Non-melanoma skin cancers:
				- Use BT with fewer fractions, especially in inoperable patients ()
		Definitive cases:
		- Avoid BT until the pandemic solves (Mohindra et al., 2020)
			Basal cell carcinoma (Exclusive):	Basal cell carcinoma:
			- Postpone according to functional risk	- Do not postpone (Chargari et al., 2020)
		Hypo-F RT can be delivered in a twice-daily frs	Until it is suitable for the institute (Barthwal et al., 2020)
		- Switch interstitial BT to EBRT
		- Switch to IORT if facilities are available (Barthwal et al., 2020)
Keloids (Exclusive)		Omit BT and consider options (Chargari et al., 2020)
Uveal Melanoma				Continue (Mohindra et al., 2020;)
Palliative		BT should be avoided and replaced by Hypo-F EBRT (Barthwal et al., 2020)

RT: radiotherapy, BT: brachytherapy, EBRT: external beam radiotherapy, HDR: high-dose-rate, LDR: low-dose-rate, SCC: squamous cell carcinoma, PPE: personal protective equipment, IORT, intra-operative radiotherapy, Hypo-F RT: hypo-fractionated RT, ISBT: interstitial brachytherapy, VVB: Vaginal vault brachytherapy.