key: cord-0899319-xeh1numh authors: Vaid, Ashok K.; Malhotra, Hemant; Thirumalairaj, Raja; Nair, Reena; Bapna, Ajay; Rajappa, Senthil J.; Somashekhar, S. P.; Goswami, Chanchal; Bajpai, Jyoti title: Indian Expert Opinion on Cancer Care during COVID-19 Pandemic date: 2021-08-21 journal: South Asian J Cancer DOI: 10.1055/s-0041-1727560 sha: f54ed92a31c693304a2c10d5ffcc801d5fa25dda doc_id: 899319 cord_uid: xeh1numh Coronavirus pandemic has increased human disease burden, as well as economic distress globally. Being in an immunocompromised state, patients with cancer comprise an important at-risk population for novel coronavirus disease 2019 (COVID-19) infection. It is necessary to modify individualized clinical management for every cancer patient in the context of the ongoing COVID-19 pandemic. Simultaneously, additional safety precautions for the cancer care providers are mandatory. This review will provide general recommendations in the Indian context optimizing the same. Public health is facing an unprecedented crisis as 7,390,702 confirmed cases of novel coronavirus disease 2019 (COVID- 19) , including 417,731 deaths, have been reported globally as of June 12, 2020. 1 Corresponding figures for India are 289,036 cases and 8,498 deaths, indicating that Indians might have a lower mortality. 2, 3 There is limited published data related to COVID-19 and cancer patients. China reported that patients with cancer had a two-fold higher chance of COVID-19 infection, several comorbid conditions (diabetes, cardiovascular diseases, and hypertension) elevating the risk. 4, 5 Another case series from Wuhan, China, showed that patients who received latest antitumor therapy within 2 weeks of COVID-19 diagnosis were more prone to develop severe events. 6 Meta-analysis of 11 studies suggested that of all patients infected with COVID-19, 2.0% had underlying cancer (95% confidence interval [CI]: 2.0-3.0%; I 2 = 83.2%). 7 The Indian Council of Medical Research (ICMR)'s laboratory surveillance for COVID-19 showed that among the COVID-19 Cancer Guidelines: An Indian Perspective Vaid et al. positive cases (n = 40,184), 25.3% were asymptomatic family contacts and 10.6% were symptomatic contacts. 8 These numbers are likely to increase and hence, India-specific cancer guidelines is the need of the hour. A group of nine Indian subject experts (medical, surgical, radiation, and hemato oncologists) met virtually (video conference) to discuss available data, personal experience, and developed the consensus review document. The draft was circulated electronically, inputs obtained and modified as appropriate, till the final document was approved by all authors. It is estimated that excess cancer deaths during COVID-19 pandemic are likely to be 6,270 in England and 33,890 in the United States. 9 Individuals at higher risk of COVID-19 infection and associated mortality among cancer cohort are summarized in ►Fig. 1. 10 The practical challenges faced by Indian oncology community and cancer hospitals are numerous. 11, 13 Several important ones are described in ►Table 1. Testing for COVID-19 among cancer patients should follow a triage system including thermal screening at point of entry, evaluation of susceptibility, and appropriate segregation bet-ween COVID-19 designated and non-COVID-19 healthcare facilities (►Fig. 2). 13, 14 The committee recommended nonsymptomatic (for COVID -19) patients to receive daycare treatment on the same day (without waiting for results of COVID-19 tests). The committee's opinion was that it was not feasible to do reverse-transcription polymerase chain reaction (RT-PCR) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) testing for all cancer patients in India, 14 limiting its application only to patients undergoing aerosol-generating procedure or those with symptoms suggestive of COVID-19 infection (such as fever, coughing, sore throat, difficulty in breathing, muscle pain, tiredness, anosmia, and dysgeusia). A separate set of recommendations should be developed by each hospital for X-ray, computed tomography (CT), pulmonary function tests, and other biological tests. All cancer patients must be told to follow prevailing government regulations against COVID-19 (including World Health Organization recommendations). 15 Management of individual cancer patients should be prioritized based on their risk category. 14 High priority: life-threatening condition, clinically unstable, and/or the benefit justifies high-priority intervention (significant overall survival gain and/or substantial improvement in quality of life [QoL]). Should continue receiving standard of care as before. Medium priority: noncritical. Delay in definitive therapy by up to 6 weeks may be permitted as appropriate without change in overall outcome. Low priority: stable. Temporarily delay anticancer management for the duration of the COVID-19 pandemic, provided there is no or low impact on survival benefit or QoL. 14 Hospital visits and elective admissions should be minimized. Noncritical elective surgical procedures, adjuvant/neoadjuvant chemotherapy, and/or radiotherapy Where treatment is to be initiated or continued, strict adherence to the COVID-19 prevention and screening strategy is mandatory. When the cancer patient is suspected or confirmed to have the COVID-19 infection, management needs to be individualized (►Fig. 3). 16 A multidisciplinary tumor board should decide whether patient has indolent/early stage disease where wait and watch policy is appropriate, whether intravenous therapies can be temporarily replaced with oral therapies, whether adjuvant therapy can allow postponement of definitive surgery, whether palliative therapy can be delayed/postponed/avoided, or whether routine follow-up visits can be postponed for asymptomatic patients who have completed their anti cancer treatment.(►Fig. 4) 14, 16 Treatment of cancer patients must not be postponed indefinitely. Remote monitoring using telemedicine should be used wherever possible. Instructions should be given to allow investigations (e.g., CBC, blood biochemistry, and CT scan) and procurement of oral medication (prescriptions) closer to home. No emergency treatment (chemotherapy, radiation therapy, or surgery) should be denied. Intensive treatment like planned allogeneic stem-cell transplantations can be delayed where disease control can be achieved with alternative treatment methods. 14 The National Institute for Health and Care Excellence (NICE) guidelines provide recommendations for prioritizing systemic anticancer therapy, radiotherapy treatments, and hematopoietic stem-cell transplantation as shown in ►Table 2. [17] [18] [19] [20] At all times, protection of the cancer care providers must be diligently followed as per prevailing regulations and standard operating procedures (SOPs). 14,21 Disruption in routine oncology services should be minimized. Awareness and screening programs should continue with the addition of education and implementation of preventive Systemic anticancer treatments 17 Radiotherapy treatments 18 Hematopoietic stem-cell transplantation 19 1 Curative treatment with a high (more than 50%) chance of success Adjuvant or neoadjuvant treatment which adds at least 50% chance of cure to surgery or radiotherapy alone or treatment given at relapse Radical radiotherapy or chemoradiotherapy with curative intent, if: • The patient has a category 1 (rapidly proliferating) tumor • Treatment has already started • There is little or no possibility of compensating for treatment gaps External beam radiotherapy with subsequent brachytherapy, if: • The patient has a category 1 (rapidly proliferating) tumor • External beam radiotherapy has already started Radiotherapy that has not started yet, if: • The patient has a category 1 (rapidly proliferating) tumor • They would normally start treatment, based on clinical need or current cancer treatment waiting times modified to make participation more patient friendly without compromising on the integrity of the study protocol. [23] [24] [25] [26] [27] Based on the ASCO suggestions, the committee recommended to (1) keep participants informed about changes to trials and their care and remind participants to alert their research team about changes to their health; (2) develop formal COVID-19 standard operating procedures for clinical trials; (3) promote telehealth virtual visits for patients; (4) implement all aspects of patient review through patient portal, email, phone, video; (5) use remote safety laboratory testing, where feasible; and (6) shipment of oral study medication directly to patients. 23 According to Globocan 2018 data, the five most common cancers in India are breast cancer (14%), oral cavity cancer (10.4%), cervix uteri (8.4%), lung cancer (5.9%), and stomach cancer (5%). Other cancers such as head and neck cancers, prostate cancer, colorectal cancer, leukemias, and lymphomas also significantly contribute to the cancer burden of India. 28 Several global organizations have published guidelines for the management of cancer patients during this COVID-19 pandemic. This committee has recommended their adoption in the Indian settings with appropriate modifications. Surgical oncology high priority includes patients who have completed neoadjuvant chemotherapy or who have progressive disease during neoadjuvant treatment, patients with breast abscess who cannot be drained at bedside, and patients whose diagnostic dilemma requires excisional biopsy. For patients with invasive cancer or those who are pregnant, a multidisciplinary tumor board will need to take individualized decision based on the risk benefit of surgery versus other modalities of treatment. Medium priority should be assigned to patients with clinically low-risk primary breast cancer (e.g., stage I/II estrogen receptor [ER]-positive/progesterone receptor [PR]-positive/human epidermal growth factor receptor 2 (HER2)-negative, and low-grade/low proliferative index tumors). They can be commenced on neoadjuvant/preoperative endocrine therapy (according to menopausal status) and definitive surgery delayed. For patients with triple-negative breast cancer or HER2-positive disease, neoadjuvant chemotherapy or HER2-targeted treatment is recommended. Low priority shall include patients with benign lesions (fibroadenomas, atypia, and papillomas), those opting for prophylactic surgery (e.g., asymptomatic with risk of hereditary cancers) and those requiring high-risk procedures (e.g., reconstruction after mastectomy). Patients with ER + ductal carcinoma in situ (DCIS) also fall in this category and their surgery may be delayed until the COVID-19 pandemic settles down. For patients with malignant phyllodes or sarcomas, decision regarding surgery needs to be individualized. [29] [30] [31] Radiation oncology of high priority includes patients requiring palliative treatment for bleeding/painful inoperable breast mass; for adjuvant postoperative radiotherapy in high-risk breast cancer patients (inflammatory disease at diagnosis, node-positive disease, triple-negative breast cancer, HER2-positive breast cancer, residual disease at surgery, and age <40 years). Medium priority should be assigned for adjuvant postoperative radiotherapy in patients with low-/ intermediate-risk breast cancer (age: 40-65 years, stage I/II luminal cancer, ER-positive, regardless of nodal status or positive margins). Use of hypofractionated regimens should be considered to reduce hospital visits. Endocrine therapy may be started during the waiting interval. Low priority patients are those with low-risk breast cancer (age: >70 years, lowrisk stage I, and ER-positive/HER2-negative breast cancer). Adjuvant endocrine therapy can be commenced while postponing radiotherapy. Locally advanced HR-negative cases may be offered neoadjuvant chemotherapy. 30 In medical oncology, oral endocrine agents, such as tamoxifen and aromatase inhibitors, can be safely continued. Patients progressing on neoadjuvant therapy should be referred to surgery, radiation, or given second-line systemic therapy. Patients with clinical anatomic stage 1 or 2 ER-positive/HER-negative should be administered neoadjuvant endocrine therapy surgery postponed for 6 to 12 months. Aromatase inhibitors should be preferred over tamoxifen for neoadjuvant endocrine therapy. The addition of oral-targeted agents to endocrine therapy may be delayed in first-line therapy or in situations where endocrine therapy alone is providing effective tumor control. Administration of granulocyte colony-stimulating factor (G-CSF) growth factor and dexamethasone should be limited, when possible. Updated Indian Association of Surgical Oncology (IASO) guidelines for head and neck cancers recommend procedures, such as tracheostomy, carotid artery ligation, or endoscopic NG tube insertion/stenting, for emergencies like stridor, bleeds, and dysphagia. Postponing of all the cosmetic reconstruction surgeries is recommended. T1 and T2 lesions should be operated with minimal hospitalization. Patients suitable for neoadjuvant therapy should be managed accordingly. Treatment of slowly progressing cancers including thyroid, parotid, and basal-cell carcinoma should be deferred. Patients with locally aggressive thyroid cancers/local invasion/airway compression should be immediately treated with surgery. Early surgery may also be considered in cases of uncontrolled hyperparathyroidism. Neoadjuvant radiotherapy and/or chemotherapy should be preferred for patients with esophagus cancers; surgery may be postponed by 3 weeks by using neoadjuvant treatment. 30 Most lung cancers are diagnosed in advanced (inoperable) stage and can be continued on standard treatment with chemotherapy, radiotherapy, and/or targeted therapy. In patients with stage-I to -III lung cancers, a multidisciplinary tumor board should decide regarding surgery. High priority for surgical oncology includes drainage ± pleurodesis for pleural effusion, pericardial effusion, tamponade risk, and evacuation COVID-19 Cancer Guidelines: An Indian Perspective Vaid et al. of empyema-abscess, T2N0 tumors, resectable T3/T4 tumors, and resectable N1/N2 disease. Medium priority is assigned to patients with resectable nonsmall-cell lung cancer (NSCLC) with T1aN0 disease, where lung nodule(s) is an incidental finding (provided solid nodule >500 mm 3 ; pleural-based solid nodule >10 mm; solid component >50 0 mm 3 in partially solid nodule; known volume doubling time <400 days, and there is new solid component in preexisting nonsolid nodule). Low-priority cases include likely benign conditions. Recommendations for medical oncology in patients with early stage, locally advanced, and metastatic lung cancers have been summarized in ►Table 3. Potential regimen alterations for NSCLC includes oral therapy (e.g., oral tyrosine kinase inhibitors [TKIs], oral etoposide, oral topotecan, and oral temozolomide) Patients with progressive disease can be evaluated with liquid biopsy instead of tissue biopsy if appropriate. 31-33 Hematological malignancies can be divided into three categories according to intent of therapy, potentially curable, controllable, and palliative. Potentially curable leukemias and high-grade lymphomas should be treated using standard protocols without compromise in dose intensity. Growth factors, as well as supportive care, must be used appropriately during therapy. The lymphoma/leukemia/myeloma treatment recommendations in the era of COVID-19 are summarized in ►Table 4. 34, 35 In patients with early-stage Hodgkin's lymphoma, baseline positron emission tomography (PET) scan and interim PET scan should be utilized to optimize the number of standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy cycles required. Intensive BEACOPP regimen (bleomycin, etoposide, doxorubicin hydrochloride, cyclophosphamide, vincristine, procarbazine, and prednisone) should be used upfront only for advanced disease or those with suboptimal response to two to three cycles of standard ABVD. Radiation therapy can be avoided and alternative regimens can be tried to reduce repeated hospital visits. In case of relapsed leukemias and lymphomas, consider the use of outpatient-based salvage therapy (e.g., • Consider deferring therapy until strongly indicated. • Consider low-dose local radiotherapy(2 3 2 Gy) for localized symptomatic disease control • Consider the use of less myelosuppressive/immunosuppressive regimens whenever possible • Refrain from anti-CD20 antibody maintenance therapy to allow for B-cell recovery Peripheral T-cell lymphoma • Standard CHOP with or without etoposide as outpatient treatment. Defer autologous HSCT indefinitely • In older patients with PTCL with a low chance of cure with multiagent regimens, consider front line therapy with novel single agents Chronic lymphocytic leukemia • Asymptomatic patients-"Wait and Watch" • If treatment initiation is required during the pandemic, an oral agent without the need for hospitalization, infusion, or frequent clinic visits would be preferred • COVID-19 negative, continue oral targeted agents but hold antibody treatments, chemotherapy, and IVIG infusions • COVID-19 diagnosis, hold CLL treatment with monoclonal antibodies and chemotherapy but consider continuing oral targeted agents in selected patients with high risk for disease flare after discontinuation Acute lymphoblastic leukemia • Curative-intent treatment of adults with ALL will require a period of inpatient management and blood product support. For a curable patient, consolidation/maintenance therapy unavoidable despite a risk of immunosuppression • Allogeneic HSCT is potentially debatable (particularly in MRD-negative CR1) and contingent upon response to therapy Acute myeloid leukemia • Curative-intent treatment of adults with AML will require a period of inpatient management and blood product support GDP-like regimens). If not feasible, decision regarding use of ICE/ESHAP/DHAP should be on case-to-case basis. Maintenance therapy with rituximab in indolent lymphomas may be postponed or temporarily held. Procedures such as high-dose chemotherapy and autologous hematopoietic stem-cell procedure must be decided in multidisciplinary tumor boards. Chronic lymphocytic leukemia (CLL) patients should be treated with oral treatments and follow-up through teleconsultation is recommended. Patients in remission for >2 years should be recommended "Wait and Watch" strategy without the need to visit the hospital. 33 Omitting, delaying, or shortening radiotherapy should be considered wherever possible. 34 Additional information, guidelines, and recommendations made by international oncology societies and bodies are also available for gastrointestinal (GI) malignancies (colorectal, pancreatic, esophageal, and hepatocellcular), sarcomas, melanomas, cervical cancers, ovarian cancers, lymphomas, NSCLC, and prostate cancers. 30, [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] In spite of all the precautions, it is possible that a cancer patient undergoing therapy might get infected with COVID-19. Such patients deserve aggressive treatment for the coronavirus infection like other noncancer patients. 45, 46 In this rapidly evolving pandemic situation, India needs to take pragmatic actions to deal with the challenges of treating cancer patients (ensuring their rights, safety, and wellbeing). Treatment decisions should be individualized based on the risk/benefit ratio for each patient. Homecare with the help of telemedicine and local physicians should be encouraged where possible. The oncology professionals are the frontline fighters who have the key responsibility of providing the best revised cancer care strategy to their patients, taking into consideration the prevailing circumstances brought about by the COVID-19 pandemic. Patients and their families should proactively participate in the decision-making process, especially by stating their preferences. Cancer patients might need additional psychological support during the COVID-19 pandemic. Ongoing clinical trials might require steps to ensure a patient friendly approach while ensuring integrity of the study data. Cancer patients need to be triaged into high, medium, or low category of risk for treatment decision-making. Telemedicine consultation services need to be ramped up to minimize hospital visits. Treatment for patients with newly diagnosed potentially curable cancer must remain a priority. Procedures with high risk of aerosol contamination must be delayed or conducted with additional precautions to safeguard the health care professionals involved. Where treatment is unlikely to improve survival meaningfully or may compromise QoL/increase risk of COVID-19 infection, a wait and watch policy can be considered. Intravenous therapies can be replaced with oral therapies if appropriate. Intensive treatment (e.g., allogenic stem-cell transplantations) should be considered only at well-equipped centers and for patients who have no other treatment options. 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Accessed April 30, 2020 41 ESMO management and treatment adapted recommendations in the covid-19 era: epithelial ovarian cancer 42 Principles for management of colorectal cancer patients during the COVID-19 pandemic Management of prostate cancer during the COVID-19 pandemic Available at: https:// www.esmo.org/guidelines/cancer-patient-managementduring-the-covid-19-pandemic/genitourinary-cancers-prostate-cancer-in-the-covid-19-era Convalescent plasma therapy for COVID-19 still has the potential to save lives -The ICMR PLACID study dissected Effectiveness of convalescent plasma therapy in Indian patients with COVID-19 There are no conflicts of interest to declare.