Core issue 5: Immunity and infection ▲ Wei Liqiang, Department of Hematology, Peking Tongren Hospital, Capital Medical University Wang Jingwen In a sense, cancer is an immunodeficiency disease, so improving the immune function of the patient is the common pursuit of both doctors and patients. It is worth noting that the NCCN has not yet taken a position on cytokine “immunity-boosting” therapies such as thymopentapeptide, which are currently prevalent in China, and the Survivorship Guidelines still advocate the use of immunization for appropriate cancer survivors. The “Survival Guidelines” still advocate the use of immunization as a “traditional method” for appropriate cancer survivors to enhance the immune system of patients, and has formulated detailed specifications for this purpose. For the first time, the guideline has elaborated on whether tumor patients need immunization, assessment of their condition, timing of vaccination, specific vaccination regimen and the safety of vaccination, and it has also given special instructions on the principles of the use of the herpes zoster vaccine. Undoubtedly, this is an authoritative specification of immunization and infection prevention for tumor patients. In clinical practice, our colleagues have not paid enough attention to this, which deserves serious reference. Tang Ligong, Department of General Surgery, Henan Cancer Hospital Immunization is beneficial to cancer survivors, who usually have or used to have immunodeficiency and become susceptible to various infectious diseases. Active immunization with vaccines can mimic the natural process of infection to produce an immune response and is not dangerous to the vaccinated person. “The Survival Guide states that patients who are eligible for immunization should receive the appropriate vaccine at least 3 weeks prior to the start of cancer treatment. Commonly used vaccines include inactivated vaccines, purified antigen vaccines, bacterial components, and genetically engineered recombinant antigens. Systematic assessment of the disease should be used to target the cancer survivor before immunization. Risk factors for infection include: underlying disease, prior chemotherapy, monoclonal antibody therapy, radiation therapy, glucocorticoid therapy, hematopoietic stem cell transplantation, previous or current exposure to endemic infectious diseases and epidemics, and history of blood transfusions. The patient’s immune system should be evaluated for a normal peripheral blood leukocyte count prior to vaccination, no current immunosuppressive therapy or chemotherapy, no current infections, and no history of allergic reactions to vaccines. Immunization regimens Although the results of vaccination are not optimal, cancer or transplant survivors should receive vaccines at routine doses and regimens if they are indicated for immunization. Vaccination regimen for all cancer survivors: The following vaccines should be administered at least 3 weeks prior to the start of cancer treatment such as chemotherapy, radiotherapy, immunosuppression, splenectomy, etc.: ☆ Trivalent Inactivated Influenza Vaccine (TIV): one dose per year. ☆ 23-valent pneumococcal polysaccharide vaccine (PPSV-23): patients <65 years of age should receive 1 dose first, and repeat 1 dose after 5 years. ☆ 13-valent pneumococcal conjugate vaccine (PCV-13): 1 dose of PCV-13 should be given at least 8 weeks prior to PPSV-23 in high-risk patients. ☆ Whooping cough - diphtheria - tetanus (Pertussis-Tetanus) vaccine: 1 dose of Pertussis-Tetanus vaccine should be given first, and then the diphtheria - tetanus vaccine should be given as a booster every 10 years. ☆ Human papillomavirus vaccine: Men and women who have not received this vaccine before should complete 3 doses of the vaccine on or before the age of 26 years. In special cases or in the presence of risk factors, the following vaccines may be given: 3 doses of hepatitis B vaccine, 2 doses of hepatitis A vaccine, Haemophilus influenzae type B (Hib) vaccine, meningococcal vaccine, typhoid fever bacillus (typhoid fever) peritrophic polysaccharide vaccine, inactivated polio vaccine, Japanese encephalitis (JE) vaccine, and rabies vaccine. Immunization Safety Vaccines to prevent infections can be challenging for cancer and transplant survivors, and vaccination of immunodeficient cancer and transplant survivors may or may not elicit a protective immune response, in addition certain live attenuated vaccines are contraindicated in immunodeficient patients. Hepatitis A vaccine, Haemophilus influenzae type B vaccine, S. typhi peripneumoniae polysaccharide vaccine, inactivated polio vaccine, Japanese encephalitis vaccine, rabies vaccine; recombinant viral antigens include Hepatitis B vaccine and HPV vaccine for men and women. Vaccines prohibited or used with caution Vaccines prohibited or used with caution for cancer survivors are mainly live attenuated vaccines, including live attenuated influenza vaccine, measles, mumps, rubella vaccine, herpes zoster vaccine, oral polio vaccine, rotavirus vaccine, oral typhoid vaccine and yellow fever vaccine. Principles of Herpes Zoster Vaccination Vaccination should be given to persons older than 50 years of age who are free of immunodeficiency, especially to cancer or transplant survivors without a history of cellular immunodeficiency, and at least 3 weeks prior to the initiation of the first chemotherapy or immunosuppressive medication. In addition, survivors of solid tumors or leukemia in remission, who have recovered immunocompetence, and who have not received chemotherapy or radiation therapy for at least the past 3 months may be vaccinated. Herpes zoster vaccine should be avoided in the following cancer and transplant survivors: patients with lymphoma; patients with malignancies affecting the bone marrow or lymphatic system; patients with a history of cellular immunodeficiency; patients who are receiving immunosuppressive therapy, including high-dose hormone (prednisone >20 mg/d or equivalent) for ≥2 weeks; and patients who are receiving or have received a hematopoietic stem cell transplant. If a person undergoing hematopoietic stem cell transplantation decides to receive herpes zoster vaccine, it should be administered at least 24 months after transplantation, in the absence of active graft-versus-host disease, and after immunosuppression has been discontinued. Core Issue 6: Pain ▲ Zhang Jianwei, Department of Oncology, Beijing General Hospital, Beijing, China The pain-related content of the NCCN guidelines is mainly distributed in three sub-guidelines – “Guidelines for Adults with Cancer Pain”, “Guidelines for Palliative Care”, and “Survivorship Guidelines”, which were released for the first time. The Adult Cancer Pain Guidelines comprehensively describe the principles of assessment and management of cancer pain (mainly pain caused by the cancer itself); the Palliative Care Guidelines focus on the management of pain in terminally ill patients; and the Survival Guidelines analyze in detail treatment-related pain. Pain in tumor patients is mainly divided into pain caused by the tumor itself and treatment-related pain, with little attention paid to the latter in the literature. In fact, about 33% of cancer survivors have treatment-related chronic pain. The reasons for the lack of effective treatment for these patients include lack of training for physicians, fear of adverse drug reactions/addiction, and inadequate medical care. The Survivorship Guidelines require cancer survivors to answer the following questions at the follow-up visit to determine if they have chronic pain that requires treatment: Is there pain? If yes, has the pain score been greater than 4 in the past month? If both questions are answered in the affirmative, further comprehensive evaluation of pain, including etiology, pathophysiology, and especially the following six categories of oncologic pain syndromes, is warranted (Figure 1). Chemotherapeutic agents such as oxaliplatin and paclitaxel often cause peripheral neuropathy, which leads to neuropathic pain; about 60% of breast cancer patients and 50% of lung cancer patients have post-surgical pain syndromes; arthralgia occurs in half of the breast cancer patients who are taking aromatase inhibitors for adjuvant therapy; pelvic radiotherapy often causes proctitis, urethritis, small bowel inflammation, vaginitis, etc., which leads to pelvic pain. For the above six types of tumor pain syndromes, the “Survival Guideline” gives a specific comprehensive treatment plan in the form of a structural diagram, recommending drug treatment, psychosocial/behavioral interventions, physical therapy/exercise and interventional therapy and other means of integrated treatment of pain. Medication includes opioids, NSAIDs, muscle relaxants, topical medications, antidepressants, anticonvulsants, glucocorticoids, and other adjunctive analgesics. Psychosocial/behavioral interventions such as relaxation training, cognitive-behavioral therapy, and physical therapy/exercise may also be effective in relieving pain. Interventions such as transcutaneous electrical nerve stimulation, intercostal nerve blocks, and intrathecal morphine injections are often used to treat refractory pain. “The Survivorship Guidelines specifically state the principles of opioid use for long-term cancer survivors: ☆ Use the lowest effective dose. ☆ Use the lowest effective dose. ☆ It is more reasonable to use the patient’s recovery of physical function as a basis for determining the effectiveness of the medication than a numeric score. ☆ Regularly evaluate the effectiveness and necessity of opioid use. If opioid-induced nociceptive hypersensitivity occurs or the medication fails to improve function, recommend gradual tapering; routinely discuss the feasibility of medication tapering; and promptly request specialty consultation. ☆ Concern about medical problems associated with long-term, heavy opioid use, such as pituitary insufficiency. The “Survivorship Guide” focuses on the pain of cancer survivors from a different perspective than before, and is bound to draw the attention of oncologists and related professionals to the chronic pain of cancer survivors, minimize the impact of pain (especially oncology treatment-related pain) on the quality of life of cancer survivors, and help patients to truly get rid of the pain of the disease and enjoy a quality life. It will minimize the impact of pain (especially tumor treatment-related pain) on the quality of life of cancer survivors, and help patients really get rid of the pain and enjoy quality life.