managemen of acute toxicities of radiotherapy.pptx

management of acute radiation toxicities is a very important topic in radiation oncology course. The patients usually present with symptoms which are to be managed by a radiation oncologist

1. Management of Acute Radiation Toxicities Dr Vikas Mohan Sharma

2. Points covered Introduction Law of Bergonié and Tribondeau Series Vs parallel organs What sequelae to expect and when Scoring systems used Radiation Dermatitis Radiation Mucositis Radiation pneumonitis Salivary Glands Larynx Radiation esophagitis Radiation Pneumonitis Heart Radiation induced GI Toxicities Radiation Cystitis Radiation induced CNS toxicities Hematologic Summary

3. Introduction S ide effects that occur on treatment or in the immediate posttreatment period Onset may be 2–3 weeks after RT S everity and timing are tied to the total biological dose and the turnover rate of the tissue in question

4. Law of Bergonié and Tribondeau In tissues with a rapid turnover rate, damage becomes evident quickly. E.g. Stem cells In tissues in which cells divide rarely, radiation damage to cells may remain latent for a long period of time and be expressed very slowly-appear more radioresistant. At a cell level survival curves may be identical, but tissue radioresponse may be very different.

5. Timing of RT-related toxicities Acute Toxicities D eath of a large number of cells. Appears in days – weeks (<3 months) Sensitive to Total dose E.g. skin, GI tract, and hematopoietic system, germinal epithelium Late Toxicities Death of slowly proliferating and differentiated cells. Appear in months or years post RT (> 6 months) sensitive to changes in size of dose per fraction . E.g. Muscle, Nerve cells, Lung, Kidney, bladder Radiation effects are commonly divided into two categories, early and late , Rapidly proliferating tissue may persist as a chronic injury – Consequential late effects. Sub acute Response : S lowly progressing damage that occurs prior to Late effects. E.g. L hermitte’s syndrome after spinal cord irradiation. somnolence after brain irradiation and subacute pneumonitis

6. Acute Reactions: U sually seen in tissues having cells with high turnover rate – GI mucosa, bone marrow, skin, oropharyngeal and esophageal mucosa. Irradiation may deplete the stem and progenitor cell pools, but nonproliferating, differentiated cells maintain tissue function until they are lost in cell turnover. The severity of radiation injury depends : dose of radiation given and fractionation schedule , treated volume and organs involved , any concomitant or previous chemotherapy given , previous surgery done having caused tissue damage individual radiosensitivity of the tissue

7. Series Vs Parallel Organs can be considered to consist of functional units arranged either in parallel (e.g. liver and lung) or in series (e.g. oesophagus and spinal cord), each with characteristic pathways to toxicity.

8. What Sequelae to Expect and When Skin changes can occur as early as within 2–3 weeks, worsen over the next 2-3 weeks then gradually resolve over the next 3–4 weeks depending on the size of field, bolus. Mucosa: Early changes start at the end of the second week, worsen by fourth or fifth week after which it gradually resolves over the next 2–3 months. CNS: Transient edema usually starts at the end of the 1 st week to tenth day of therapy Somnolence appears at 4–5 weeks. M ild behavioural changes or short-term memory loss which may take up to 2–3 months post-therapy. Esophagus: Esophagitis usually starts after completion of 3 rd or 4 th week of therapy and can worsen towards the end of treatment. R esolves over the next 6–7 weeks. Enteritis: starts towards end of fourth or fifth week of therapy and can resolve over the next 4–5 weeks. Cardiac: Most of these effects are typically late effects >1yr. Cystitis, Proctitis: These reactions are generally noted after fourth week and resolve over the next 4–7 weeks.

9. Scoring Systems for Tissue Injury Late Effects of Normal Tissue, Subjective Objective Management Analytic (LENT-SOMA) (1992): Toxicities are graded 1–5, where 1 is asymptomatic or minimally symptomatic and 5 is complete loss of organ function. Rarely used in modern protocols. RTOG Common Toxicity Criteria (CTC) (1995): Graded all toxicities 1–5, where 1 is asymptomatic or minimally symptomatic and 5 is death. RTOG CTC only applies to radiation toxicities. Toxicities classified into “Early” and “Late” Common Toxicity Criteria (CTC) v2.0 (1999): Added chemotherapy toxicities. Common Toxicity Criteria for Adverse Events (CTC-AE) v3.0 (2003): Much longer and more detailed than CTC v2.0. Includes “adverse events” other than treatment toxicities, such as comorbid medical and psychiatric events, motor vehicle accidents, etc. Common Toxicity Criteria for Adverse Events (CTC-AE) v4.0 (2009): This version is up to 764 categories and 195 pages long. CTC-AE V 5.0 (2017) – 54 new/updated algorithms were added in 19 lab parameters

10. Radiation Dermatitis R esults from injury to the rapidly dividing cells of the dermis, epidermis and feeding vasculature Pathogenesis: Damage to Basal keratinocytes, do not allow time for basal skin cells to replenish in order to maintain optimal renewal of the epidermis Transforming growth factor (TGF)-beta, whose levels are increased within hours of radiation exposure, is thought to be implicated in the late radiation-induced fibrotic changes

11. CTCAE criteria (v5.0) Grade - 1 Grade - 2 Grade - 3 Grade - 4 Follicular, faint or dull erythema / epilation / dry desquamation / decreased sweating Tender or bright erythema, patchy moist desquamation / moderate edema Confluent, moist desquamation other than skin folds, pitting edema Ulceration, hemorrhage , necrosis

12. Management The management of radiation dermatitis is guided by the severity of skin damage. Pre radiation assessment: History and physical examination. Screen for hypersensitivity syndromes ( Toxic epidermal necrolysis , Steven Johnson Syndrome) Rule out any collagen vascular disease ( SLE ,Scleroderma) History of Ataxia telangiectasia, Fanconi anemia. Nutritional status of patient. History of diabetes, obesity and Smoking status

13. General skin care Maintaining the irradiated area clean and dry. Washing with lukewarm water and mild soap (synthetic soaps are preferable). Using unscented, lanolin-free, water-based moisturizers two to three times per day, including nontreatment day on the weekend. Avoiding skin irritants, such as perfumes and alcohol-based lotions. Wearing loose-fitting clothes to avoid friction injuries. Avoiding sun exposure. Avoiding wet shaving within the treatment area; an electric razor is a safe alternative.

14. G rade-1: radiation dermatitis usually do not require any specific treatment in addition to general skin care measures. Grade-2: moist environment promotes the rate of re-epithelization and increases the speed of wound healing Topical corticosteroids, nonadherent, hydrogel, or hydrocolloid dressings Grade 3 radiodermatitis with moist desquamation may require interruption of radiation therapy, depending upon the body location and the patient's discomfort. Grade 4:dermatitis is rare. Surgical debridement, full-thickness skin graft, or myocutaneous or pedicle flaps. For infected or at-risk wounds, systemic or topical antibacterial agents should be considered. Patients receiving cetuximab  — In patients receiving concurrent  cetuximab  therapy who develop grade 1, 2, or 3 radiation dermatitis, interruption or dose reduction of cetuximab is not generally necessary. If Gr-4 toxicity develops, cetuximab should be interrupted until Gr-2.

15. Topical corticosteroids  — for the prevention of severe radiation dermatitis and the reduction of discomfort and itching. Low- to medium-potency topical corticosteroids, such as  mometasone  furoate 0.1% or  hydrocortisone  1% cream, are applied to the treatment field once or twice daily, after each radiotherapy session. Conclusion:  T opical corticosteroids can be effective in reducing the incidence of wet desquamation and lessen the mean RD scores . The use of topical corticosteroids can reduce pruritus in participants and improve quality of life.

16. Spectrum of problems arise if dental care is compromised   a. Mucositis b. Xerostomia c. Radiation-associated caries d. Oral candidal infections e. Loss or alteration of taste and weight loss f. Trismus g. Osteoradionecrosis

17. Radiation Mucositis R esults from progressive vaso -congestion and oedema of the mucosa accompanied by erosion and denudation of the surface epithelium A ffects the mouth, pharynx, oesophagus, and other gastrointestinal organs Severe cases progress to ulceration with pseudomembrane formation and constant pain I ncreases the risk of infection due to disruption of the mucosal barrier The resultant pain and dysphagia affect oral intake and nutrition

18. Pathogenesis of oral Mucositis DOI: 10.1177/0022034516641890 1 st WEEK 2 nd -4 th WEEK > 5 th WEEK Post Rx

19. Irritation / may experience mild pain not requiring analgesic Patchy mucositis that may produce an inflammatory serosanguinous discharge / may experience moderate pain requiring analgesia Confluent fibrinous mucositis / may include severe pain requiring narcotic Ulceration, hemorrhage or necrosis

20. Treatment Role of Safe Radiotherapy: -Intensity-Modulated Radiation Therapy (IMRT), and - simple, custom-made, intraoral devices (palatal shield) that are designed to exclude uninvolved tissues from the treatment portals or to provide shielding of tissues within the treatment area. - Packing gauze between mucosa of the lateral tongue and buccal area appears to be very beneficial in minimizing the dose from scattered radiation. Nutritional Support: A soft diet or liquid diet was more easily tolerated than a normal diet, when oral mucositis is present; NG tube is more beneficial, when there is severe mucositis. The RTOG guidelines: brushing with a soft toothbrush, flossing, and the use of nonmedicated rinses (for example, saline or sodium bicarbonate rinses). Patients and caregivers should be educated regarding the importance of effective oral hygiene.

21. Steps (Drugs/Intervention) for prevention of Mucositis: Encourage to maintain oral hygiene, use brush with soft bristle, dental evaluation should be done prior to radiation 1.1% NaF containing tooth paste should be used Encourage use of tooth brush at least 3-4 times a day, particularly after a meal. Lips should be moistened with water based lubricants (oil based should not be used as it may increase chance of infection) Encourage to take liquid, semi-solid food, rich in protein (2 gm/kg) and containing Vit B and Vit C. Food with high sugar, acid, spices, hot temperature and dry or coarse food should be avoided. Benzydamine mouthwash be used to prevent oral mucositis in patients with head and neck cancer receiving moderate dose radiation therapy (up to 50 Gy), without concomitant chemotherapy

22. Steps to treat Mucositis: Interruption of radiation and restart at the earliest, if Grade III mucositis, preferably interrupt at the week end Revisit the planning for a possible modification OR re-planning as required Pain management: Local analgesia should be preferred over systemic Local anesthetic -lignocaine Topical rinse-including aspirin and 0.5% doxepin mouthwash Opioids: 2% morphine mouthwash Treatment of coexisting infection/control of oral candidiasis In suspected infection take a swab and send for culture For bacterial infection Gram positive and anaerobic coverage is important and Amoxicilin+Clavulenic acid 625 mg PO or 1.2 gm IV TDS with Metrogyl 500 mg PO BD OR 400 mg IV BD should be used For suspected Candida infection Clotrimazole lozenges should be used

23. Bezydamine mouth gargle 5ml in equal water every 4 hours. The rinse should last for at least 5 minutes every time. [Chlorhexidine mouthwash not be used to prevent oral mucositis] Consider restarting radiation by the next week so that the treatment interruption is minimum Criteria to consider stop course of radiotherapy: Eg : Grade 3 Mucositis with > 2 fractions left for completion of treatment ( Will vary from patient to patient though) Emami et. al TD5/5 = 32Gy, TD50/5 = 46Gy QUANTEC Mean <45Gy

24. Salivary Glands Pathology: Damage to acinar cells, stem cells, membrane receptors Symptoms: dryness of the mouth and lips, increased thirst, altered taste, difficulty in swallowing solid food, fissures at lip commissures, burning sensation of the tongue, a dorsal tongue surface atrophy. C ompromised buffering capacity by saliva leading to a propensity for oral infections, increased risk of dental caries, difficulty in wearing dentures, and progressive periodontal disease. The decrease in the salivary flow begins within the first week of RT and persists several months to years. In most cases xerostomia is irreversible The recovery of the gland may occur within approximately 2 years after RT, with a possible 30% increase in salivary function within 5 years. Prevention: Amifostine It is a free radical scavenger . administered just prior to each RT fraction. Reduced acute and chronic grade 2 or higher xerostomia when administered concurrently with RT in a randomized phase III trial. ( Equals by reducing 9Gy mean dose to parotid and submandibular glands.)

25. F irst phase (10 th day of RT) –Rapid fall of flow rate of saliva S econd phase (10 th day to 2 nd month): reduction in the amylase secretion in addition to a reduction in the number of functioning acinar cells. T hird phase (2–4 months post-RT): Severity of symptoms aggravates Fourth phase (4–6 months and beyond, post-RT): Deterioration of gland function. difficult and painful swallowing and chewing, loss of taste and digestion, resulting in poor oral hygiene and predisposing to oral and dental infections.

26. Salivary gland Grade-1 Grade-2 Grade-3 Grade-4 Mild mouth dryness / slightly thickened saliva / metallic taste / these changes not reflected in alteration in baseline feeding behavior, such as increased use of liquids with meals Moderate to complete dryness / thick, sticky saliva / markedly altered taste - Acute salivary gland necrosis ACUTE

27. Treatment Salivary substitutes that temporarily hydrate the mucosa: Ingredients such as hyetellose , hyprolose , or caramellose . Gustatory stimulants: Acidic, bitter, or sweet substances such as citrus flavors or cough drops. Xylitol, a sugar substitute used in gum and lozenges, may have positive effects on dentition. Pharmacologic stimulants are generally parasympathomimetic agents: Bethanechol, pilocarpine, and cevimeline. Common side effects include sweating, dizziness, headache, nausea, flushing, and increased urge to urinate . QUANTEC recommends a mean dose of <20 Gy to one parotid gland or <25 Gy to both parotid glands to avoid severe xerostomia which is defined as a long-term salivary function <25% of baseline. Deasy JO, Moiseenko V, Marks L, et al.

28. Larynx: Laryngeal edema, aspiration, and vocal dysfunction are the endpoints of laryngeal irradiation. Radiotherapy induces sterile inflammation. p 53 mediated apoptosis, secondary apoptosis causes inflammation, hyperemia, and erythema of the laryngeal mucosa. Late radiation toxicity may be caused by extensive fibrogenesis. Laryngeal Mucositis : Pain : NSAIDs, opiates. – Mild: Ibuprofen. 200–800 mg po q4–6 h. Max 3200 mg/day. Naproxen. 250–500 mg po bid. Max 1500 mg/day. – Severe: Fentanyl transdermal. 25–100 μg/h patch q72 h. Voice changes : glandular atrophy results in poor lubrication. Changes include reduced vocal loudness, low modal speaking pitch, reduced phonic changes, hoarseness, and vocal fatigue. Management - Voice therapy following chemoradiotherapy focuses on vocal hygiene .

29. Larynx Grade-1 Grade-2 Grade-3 Grade-4 A CUTE Mild or intermittent hoarseness / cough not requiring antitussive / erythema of mucosa Persistent hoarseness but able to vocalize / referred ear pain, sore throat, patchy fibrinous exudate or mild arytenoid edema not requiring narcotic / coughrequiring antitussive Whispered speech, throat pain or referred ear pain requiring narcotic / confluent fibrinous exudate, marked arytenoid edema Marked dyspnea, stridor or hemoptysis with tracheostomy or intubation necessary

30. Edema: may occur 2–3 weeks of radiation. The incidence of laryngeal edema increases with total radiation dose, field size, tumor stage, smoking, and chemotherapy administration. Usually recovery begins 3 weeks after treatment and may require 6–12 months to subside. Conservative management includes voice rest, the use of antibiotics for ulceration and possibly steroids. Persistence of edema longer than 3 months after radiotherapy is an indicative of recurrent or persistent tumor. Laryngectomy may be needed for management of laryngeal edema for these patients.

31. Dysphagia Assessment and Management Pharyngeal Constrictor Muscles: The pharynx extends from the base of the skull to the cricoid cartilage. Dysphagia may develop due to radiation-induced normal tissue changes including edema , neuropathy, and fibrosis. Contouring : The cranial border was defined as the caudal tip of pterygoid plates , occipital condyle , or the level of C1–C2 interspace and caudal border as the lower edge of the cricoid cartilage. Prevention is the most effective approach and is achieved with careful treatment planning.

32.   All Head and neck cancer patients are to be evaluated for baseline swallowing function and nutritional status. All patients should undergo dietician evaluation during treatment Methods to assess baseline Dysphagia :   History and clinical examination: Royal Brisbane Outcome Measure for Swallowing (RBHOMS) 2. Criteria for prophylactic Naso -gastric tube placement:(Any one or more) Baseline measured weight loss > 10% (Objective measurement) Body mass index < 18 kg/m2 RBHOMS level < 5 (Refer Table above) Grade 3 or higher dysphagia (RTOG)

33. RTOG Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Implication Pharynx and esophagus Mild dysphagia or odynophagia / may require topical anesthetic or non-narcotic analgesics / may require soft diet   Moderate dysphagia or odynophagia / may require narcotic analgesics / may require puree or liquid diet Severe dysphagia or odynophagia with dehydration or weight loss > 15% from pretreatment baseline requiring NG feeding tube, IV fluids, or hyper alimentation Complete obstruction, ulceration, perforation, fistula Death Consider stopping radiotherapy at Grade 3 or higher toxicity

34. Esophagus Radiation induced esophagitis is usually self-limiting. Pathology: Capillary pericyte damage + Basal layer damage. its severity may interfere with treatment course, leading to treatment delays, hospitalization, or interruption of RT Clinical presentation: dysphagia or odynophagia, may lead to weight loss and/or dehydration. In rare cases, perforation or obstruction . Symptoms of acute esophagitis usually slowly resolve within 2 to 3 weeks after completion of RT. stricture formation – Late toxicity During treatment planning, it is advised to minimize esophageal exposure as is possible (without compromising target coverage). IMRT might be an effective way to minimize eso phageal exposure

35. Oesophagitis usually starts after completion of the 2 nd -3 rd week of therapy, usually at a dose of 20–30 Gy. symptoms can resolve mostl y by the end of 2 nd month post radiotherapy. Pharynx & esophagus Mild dysphagia or odynophagia / may require topical anesthetic or non-narcotic analgesics / may require soft diet Moderate dysphagia or odynophagia / may require narcotic analgesics / may require liquid diet Severe dysphagia or weight loss > 15% from pretreatment baseline requiring NG feeding tube, IV fluids, or hyperalimentation Complete obstruction, ulceration, perforation, fistula Grade-1 Grade-2 Grade-3 Grade-4

36. Treatment/Prevention Recommendations - Elevation of head end of bed while in supine position to prevent aspiration. Decreased gag reflex. - Putting in a Ryle’s tube for aspiration if required or maintaining nutrition by a feeding gastrostomy/jejunostomy. - Providing high-calorie, high-protein liquid or semisolid diet composed either of medicinal preparations or bland food which is soft in consistency. - Avoid irritant food and consider behavioral changes (stop smoking , avoid alcohol, coffee, acidic and spicy food) - Consider dietician referral, encourage use of small, frequent meals, soft diet. weight to be monitored on a weekly basis. - Consider antacid to decrease acid reflux and PPI at first symptoms of esophagitis. - Combination of antacid (sucralfate may be prioritized in patients with no nausea and vomiting) with topical analgesics (viscous lidocaine - Nystatin solutions may be considered as prophylaxis. Oral antifungals may be required for refractory cases - After establishment of esophagitis support nutrition with oral supplements, i.v. hydration - Opioid analgesics (tramadol, f entanyl )

37. Radiation pneumonitis Caused by endothelial damage and congestion of delicate alveoli, impairing gas exchange, along with an exudative, inflammatory cascade of cytokine-mediated fibroblast proliferation and fibrosis In the subacute setting, TGF- β and IL-6 is thought to be responsible

38. RILI incidence lung cancer (5%-25%) mediastinal lymphoma (5%-10%) and breast cancer (1%-5%). Symptoms: Pneumonitis — Dry cough (or productive sometimes of thick white sputum), shortness of breath, increased oxygen requirements, pleuritic chest pain, and/or pyrexia; Presentation with acute injury-Radiation pneumonitis (RP): <6months chronic injury- RPF starts 6–24 months after exposure. Preventive measures : adherence to RT dose/volume constraints, fractionation, RT techniques, and P harmaceutical prevention – e.g. Amifostine , Pentoxifylline, Captopril, Palifermin.

39. R adiologic finding: ill-defined or straight edged fibrosis, scarring +/- traction bronchiectasis .

40. Treatment: dependent on the patients’ symptoms. If other differentials are ruled out, then start Tab PREDNISOLONE 1 mg/kg/day (Max – 60 mg) in divided doses BD for 4 weeks followed by tapering of dose Anti-oxidants like alpha tocopherol Anti- tussives like dextromethorphan syrup ( 1 tsp Q6H) Anti- allergics like ( levo ) cetirizine tablets Tab Pentoxiphylline 400 mg TDS for 8 weeks may be considered If obstructive features on PFT, start salbutamol and ipratropium nebulisation. Recall RP : in whom the lung was exposed to radiation, symptoms of RP may sometimes appear to be brought on by the subsequent receipt of a systemic agent. eg , etoposide, gemcitabine, Adriamycin, paclitaxel, pemetrexed in case of suspicion of “recall RP,” the trigger medication should be stopped and, if needed, treatment as noted earlier for RP be considered.

41. Heart The most common radiation-induced heart injury is acute pericarditis, which seldom occurs during the first year posttherapy. A dose of 45 to 50 Gy in conventional fractions produces an 11% incidence. Radiation induced cardiovascular disease (RICVD) comprises different disease entities such as pericarditis, cardiomyopathy, valvular heart disease, and coronary heart disease. Symptoms: chronic pericarditis, coronary artery disease, restrictive cardiomyopathy (diastolic dysfunction), congestive heart failure with a preserved ejection fraction, valvular dysfunction, and conduction disorders Timing: 5 to 30 years

42. HEART Grade-1 Grade-2 Grade-3 Grade-4 A CUTE Asymptomatic but objective evidence of EKG changes or pericardial abnormalities without evidence of other heart disease Symptomatic with EKG changes and radiological findings of congestive heart failure or pericardial disease / no specific treatment required Congestive heart failure, angina pectoris, pericardial disease responding to therapy Congestive heart failure, angina pectoris, pericardial disease, arrhythmias not responsive to nonsurgical measures

43. Prevention: Ensure that dose to the heart is as low as possible. Encourage lifestyle modifications (smoking cessation, diabetes control, weight loss, dietary modifications, and exercise) Recommended prophylactic/screening for symptoms Echocardiogram C onsider techniques DIBH when ever available.

44. Management: treatment options in order of recommended use/increasing symptom toxicity. Refer to a cardiologist if heart failure or coronary artery disease is suspected. Acute pericarditis: incidence is rare. NSAIDS or colchicine , Cardiologist referral. Radiation induced cardiomyopathy : Irreversible damage . ACE inhibitors, angiotensin receptor blocker, beta blocker, diuretics, isosorbide dinitrate, and digoxin. Severe cases may require C ardioverter-defibrillator and Heart transplantation Coronary heart disease (CHD) : Angina pectoris in a patient irradiated to the chest requires attention and immediate coronary angiography is advised.

45. Gastrointestinal Toxicity Acute Toxicity : presents as nausea, diarrhea, cramping, and abdominal pain starting from the third or fourth week of pelvis radiotherapy Check list prior starting RT: diabetes , atherosclerosis, or inflammatory bowel disease . History of abdominal surgery

46. Radiation induced nausea & vomiting Due to increased reflux, - gastric and enteric stasis, - an increased turnover of mucosal cells, - decreased gut motility due to peripheral nerve sheath inflammation - even triggering of central pathways by vagal stimulation. Treatment: Prophylactic recommendations High Risk (Total body irradiation) 5-HT3 RA + Dexamethasone Moderate risk (Upper abdomen, CSI) 5-HT3 RA ± Dexamethasone Low Cranium: Dexamethasone Head and neck, Thorax, pelvis: Dexamethasone or Dopamine RA or 5-HT3 RA Minimal (Extremities, Breast) Dexamethasone or Dopamine RA or 5-HT3 RA

47. Upper GI Grade-1 Grade-2 Grade-3 Grade-4 Upper GI (ACUTE) Anorexia with ≤ 5% weight loss from pretreatment baseline / nausea not requiring antiemetics / abdominal discomfort not requiring parasympatholytic drugs or analgesics Anorexia with ≤ 15% weight loss from pretreatment baseline / nausea and/or vomiting requiring antiemetics / abdominal pain requiring analgesics Anorexia with > 15% weight loss from pretreatment baseline or requiring NG tube or parenteral support. Nausea and/or vomiting requiring tube or parenteral support / abdominal pain, severe despite medication / hematemesis or melena / abdominal distention (flat plate radiograph demonstrates distended bowel loops) Ileus, subacute or acute obstruction, perforation, GI bleeding requiring transfusion / abdominal pain requiring tube decompression or bowel diversion

48. Lower GI Grade-1 Grade-2 Grade-3 Grade-4 Lower GI / Pelvis Diarrhoea (ACUTE) Increased frequency or change in quality of bowel habits not requiring medication / rectal discomfort not requiring analgesics Diarrhea requiring parasympatholytic drugs (e.g. Lomotil) / mucous discharge not necessitating sanitary pads / rectal or abdominal pain requiring analgesics Diarrhea requiring parenteral support / severe mucous or blood discharge necessitating sanitary pads / abdominal distention (flat plate radiograph demonstrates distended bowel loops) Acute or subacute obstruction, fistula or perforation; GI bleeding requiring transfusion; abdominal pain or tenesmus requiring tube decompression or bowel diversion

49. Management A nti -nausea and antacid medication prophylacticall y. Dietary modifications, fiber supplements, or probiotics can all be used . Antidiarrheal agents should be prescribed at the first sign of loose stools, take upon awakening, and 30 minutes before each meal daily . loperamide may bring down frequency and severity of loose motions. First loperamide should be started every 2–3 hourly for a maximum of 48 h. If the diarrhoea has not responded, then switch to octreotide at dose of 50 μg SC every 8 h, and increase dose to 100 μg if response not noted. Antibiotics are rarely required. Abdominal cramps are common and can be treated with dicyclomine. Patients with refractory enteritis- should be monitored for hydration status, malabsorption (Vitamin B-12, Bile salts).

50. Steps for Prevention of Diarrhea Belly Board Device (BBD) with patient in prone position considered   Early dietary counselling Home-made foods like porridge and daliya . Eliminating all lactose-containing products and high osmolar dietary supplements Small and frequent meals encouraged. Advise to include green leafy vegetables, fruits and intake of high fibres in diet.  Probiotics One sachet TDS of VSL#3- starting from the first day of radiation therapy until the end of the scheduled fractions of radiation therapy can be considered * Each sachet of VSL#3 contained 450 billions/g of viable lyophilized bacteria , including four strains of lactobacilli (L. casei , L. plantarum, L. acidophilus, and L. delbruekii subsp. bulgaricus), three strains of bifidobacteria (B. longum , B. breve, and B. infantis ), and one strain of Streptococcus salivarius subsp. thermophilus.

51. Management of Uncomplicated Mild to Moderate Diarrhoea: Dietary modifications ( eg , eliminating all lactose-containing products and high osmolar dietary supplements) Loperamide : Initial dose of 4 mg followed by 2 mg every 4 hours or after every unformed stool (not to exceed 12 mg/d) . Management of severe Diarrhoea: If not responding to Loperamide. Hospital admission is required. Stop Radiation till symptomatic improvement, Assess hydration status, electrolytes, nutritiona l status.- start i.v fluids (0.9% NS), Correct Electrolyte imbalance , probiotics, anti cholinergics (Lomotil)- assess for any contra indication, i.v antibiotics if necessary avoid lactose rich foods. Analgesics for Abdominal cramps,

52. Patients should be encouraged to drink a minimum of 2.5–3 L of fluids per day. Foods rich in roughage and calcium as well as potassium should be advised. Milk and milk products are usually avoided as lactase deficiency can lead to lactose intolerance. Recent recommendations state that sulfasalazine taken orally twice a day reduce the incidence and severity of radiation-induced bowel changes. Hospitalization may be required in severe toxicity cases.

53. Genitourinary Toxicity - Bladder is a late responding tissue with a latency of several months. - Loss of bladder surface cells causes irritation and proliferation of deeper stromal cells such as fibroblasts. This leads to irritability, fibrosis, and progressive reduction in bladder capacity. - Obesity and heavy smoking have also been documented as risk factors for bladder complications following RT for cervical cancer. Acute Toxicity : including dysuria, urinary frequency, nocturia, and hesitancy, Acute urinary retention is a rare complication

54. Grading Of Radiation Cystitis

55. Management For acute symptoms, a workup is indicated that include urinalysis and urine culture to exclude other causes of urinary symptoms. If Positive for Dipstick test, Complete course of antibiotics as per c/s. If Dipstick test negative start conservative management of symp t oms that include N SAIDS , anticholinergic agents (oxybutynin) , or analgesics such as phenazopyridine. Bladder spasms: Tolterodine (2 × 1–2 mg), oxybutynin (2–3 × 5 mg) or flavoxate ( 100mg TDS ), trospium chloride (3 × 15–30 mg). Remember to check if patient has any contraindications to the drugs and explain anti-cholinergic side effects. Encourage patient to take 2.5 to 3 L of water each day and use urine alkaliniser

56. CNS Toxicities Three main categories of cells are involved: neurons, vascular endothelial cells, and glial cells. The most important injuries to the brain by radiation are all late syndromes Toxic ities depend on total dose, fractionation schedule, and volume treated . Pathogenesis: Vascular Endothelial injury, Axonal demyelination, Coagulative necrosis of white matter. Over production of myelin in oligodendrocytes and occurs as a late toxicity- Leukoencephalopathy. Demyelination can also occur in spinal cord and nerve roots.

57. Brain Acute fatigue, somnolence syndrome cognitive alterations in short-term memory and concentration , Pituitary dysfunction resulting in endocrinological disruptions, Dementia – rare cases The subacute constellation of fatigue, lethargy, clumsiness, and cognitive decline is termed somnolence syndrome. fatigue begin to increase roughly halfway through the treatment and peak at the end of treatment.

58. Radiation-Induced Edema and Radionecrosis : The classic description on MRI is a “soap bubble” or “swiss cheese” appearance damage to vascular endothelial cells and glial cells resulting in a local inflammatory cascade involving HIF1-alpha . decreased regional cerebral blood volume ( rCBV ). Surgical resection or biopsy remains the gold standard. N ever seen in patients treated solely with fractionated whole-brain radiation For partial-brain irradiation, a dose-toxicity relationship is evident as well. TD 5/5 – 45 Gy to Whole brain TD 50/5- 60 Gy to 1/3 rd brain. Management: generally includes initial conservative management with steroids and serial imaging. Progressive lesions:-resection, and antiangiogenic therapy with bevacizumab or hyperbaric oxygen, Anticoagulation therapy. Pseudoprogression - Edema masking the disease progression during post treatment.

59. Hematopoietic Hematopoietic stem cells (HSCs) are among the most radiosensitive cells in the body. Total Body Irradiation : Hematopoietic tolerance is a LD50 of 3–4 Gy in a single fraction, without stem cell transplant. The purpose of myeloablative conditioning for stem cell transplant is to ablate the host’s HSCs. Therefore TBI doses exceed HSC tolerance. Partial Body Irradiation: Death of HSCs in one part of the body induces accelerated growth and differentiation of hematopoietic cells elsewhere in the body. Heavily irradiated bone marrow (>30 Gy) may never fully recover. This may be seen as abnormal marrow signal on MRI persisting for many years. Extramedullary hematopoiesis (spleen, liver, soft tissue) may occur.

60. Differential Effects by Cell Lineage: Lymphocytes (including plasma cells) are the most sensitive and nadir within hours to a few days. Unlike the other lineages, even mature lymphocytes are radiosensitive due to apoptosis. Granulocyte lineage is intermediate in sensitivity. Only the stem cells are killed, the differentiated cells continue their normal lifespan, with a nadir at 2–4 weeks. Platelet lineage is somewhat less sensitive, and platelets also nadir at 2–4 weeks. Red blood cell lineage is relatively radioresistant. Hemoglobin is largely unaffected by TBI unless bleeding occurs.