Hodgkin's+Disease+(Adult+&+Child)

-Patients may present exclusively with constitutional symptoms in the absence of any physical findings, known as B symptoms. B symptoms include: fever, unexplained weight loss (10% in six months Chao) and drenching night sweats. Patients can also present with generalized pruritus (associated with a poorer prognosis, noted in approximately 10 to 15 % of patients) and alcohol inducing pain in tissues involving Hodgkin’s disease. 2 -80% of patients present with cervical lymph node involvement. 1 -50% of patients present with mediastinal disease: These patients may present with associated symptoms of shortness of breath, chest pain, cough and/or superior vena cava syndrome. 2 || -An evaluation of all nodal sites is mandatory. -For patients that will receive radiation therapy it is advised to have a dental exam. -Laboratory tests: a complete differential blood count, erythrocyte sedimentation rate (ESR), serum electrolytes, liver and renal function tests, serum alkaline phosphatase, and beta2-lactate dehydrogenase. Optional but useful tests include: serum copper, microglobulin, and various surface cytogenetic analyses. 1 -Radiology studies: Posteroanterior and lateral chest radiographs are needed with measurements of the tumor mass: thoracic ratio at either T5-6 or at the diaphragm and Computed Tomography (CT) scans of the chest, abdomen and pelvis. In reviewing the chest CT scan, evaluation of the mediastinal disease extent, axillary involvement, pericardial nodal involvement and chest wall invasion are completed. The baseline nuclear medicine scan used is F-fluorodeoxyglucose positron emission tomographic (FDG-PET) scanning (more sensitive to both initial staging and follow-up of Hodgkin’s disease.  2 - Pathological evaluation: Bone marrow biopsies are limited to patients with advanced stage disease and/or constitutional symptoms. Excisional biopsies are done, depending upon location of the disease. 2 -Pretreatment baseline evaluation: Patients receiving Adriamycin need a baseline MUGA scan. Patients receiving bleomycin need baseline pulmonary tests. 2 || -Lymphocyte-predominant (LPHD) (most favorable) -Nodular-sclerosing (NSHD)(most common and less favorable than LPHD) -Mixed-cellularity (MCHD)( less favorable than NSHD) -Lymphocyte-depleted (LDHD) (worst prognosis)
 * Epidemiology: || Hodgkin's Disease makes up 14% of lymphomas. 6  It is more common in males than females, and it is more frequent in developed countries than underdeveloped countries. As of now, there is no explanation for these statistics. Hodgkin's Disease occurs in young people, most commonly between the ages of 11 and 30, with a median age of 26 years at the time of diagnosis. There is another peak of incidence that takes place between 75 and 80 years of age. It is rare in children under 10. 7 ||
 * Etiology: || The etiology of Hodgkin's Disease is unknown. There is no clear relationship with environmental exposures, although an increase has been reported in wood workers, farmers, and meat workers. Although no specific pathogen has been identified to help in the diagnosis of Hodgkin's, the best candidate is Epstein-Barr virus (EBV). People with a history of infectious mononucleosis have a threefold chance of developing Hodgkin's. However, many patients with the disease show no signs of EBV or infectious mononucleosis. 6  In fact, most cases in the United States are not EBV related. 7 There seems to be an increased frequency in patients with AIDS. In these patients, the disease tends to involve extra nodal sites and exhibits an aggressive clinical course with a poor outcome. 6  Another risk factor for Hodgkin's is defective T-cell functioning. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">7 ||
 * Signs & Symptoms: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 11pt; line-height: 200%;">“Patients with Hodgkin’s disease generally present with painless lymphadenopathy.” 1
 * Diagnostic Procedures: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-A diagnostic workup begins with a complete physical examination including any documentation of any B symptoms and other symptoms such as pruritus intolerance, fatigue, respiratory problems and alcohol intolerance.
 * Histology: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">Four histological subtypes of Hodgkin's disease (HD) are defined by the Rye modification of the Lukes and Butler System:

"The neoplastic cell of HD is the Reed-Sternburg cell. It is typically binucleate, with a prominent, centrally located nucleolus in each nucleus. It also has a well-demarcated nuclear membrane and eosinophilic cytoplasm with a perinuclear halo." <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> 1 || Spread to the viscera occurs after spread to the adjacent lymph nodes. Obviously, visceral spread indicates a higher stage and worse prognosis. The spleen becomes involved in late stages, and the likelehood of disseminated disease increases with splenic involvement. The liver and/or bone marrow are at increases risk with splenic involvement. Hodgkin's disease can also spread to the lungs and skeletal system in late stages. It rarely involves the organ systems of the upper aerodigestive tract, central nervous system (CNS), skin, gastrointestinal (GI) tract, Waldeyer's ring, or Peyer's patches. 5 ||
 * Lymph Node Drainage: || <span style="color: #ff0000; font-family: 'Times New Roman',Times,serif; font-size: 12pt;">Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph. 8 ||
 * Metastatic Spread: || Hodgkins disease has a predictable pattern of spread, and 90% of the patients have contiguous spread. In other words, the cancer has begun spreading to the adjacent node of region. The rapidity of the growth and spread of the disease, however, are not predictable.
 * Grading: || Four histologic subtypes of HD are defined by the Rye modification of the Lukes and Butler system.

Lymphocyte-predominant HD (LPHD) is often diagnosed in young people. Patients frequently present with early-stage disease, and systemic symptoms are uncommon (less than 10%). The natural history is most favorable of the histologic subtypes. Nodular-sclerosinh HD (NSHD) is the most common histologic subtypes. The mediastinum is often clinically involved. One-third of these patients have B symptoms. The natural history of NSHD is less favorable than that of LPHD. In mixed-cellularity HD (MCHD) patients more commonly present with advanced disease. Its natural history is less favorable than that of NSHD. Lymphocyte-depleted HD (LDHD) tends to occur in older patients and is more likely to be associated with advanced disease and B symptoms. It has the worst prognosis of all histologic subtypes of HD. 5 ||
 * Staging: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The Ann Arbor staging system has been used for Hodgkin's disease since 1971. This system designates a clinical stage based upon results of the clinical staging studies, initial biopsy, pathologic stage, as well as any later biopsies. "Inadequacies of the Ann Arbor system include failure to consider bulk of disease and lack of a more precise definition of the E lesion."

Stage I--involvement of a single lymph node region Stage II--Involement of two or more lymph node regions on same side of diaphragm (II) or localized involement of an extralymphatic organ or site and of one or more lymph node regions on same side of diaphragm (IIE) Stage III--Involvement of lymph node regions on both sides of diaphragm (III), which may also be accompanied by involvement of spleen (IIIS) or by localized involvement of an extralymphatic organ or site (IIIE) or both (IIISE) Stage IV--Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">1 || menopausal symptoms in women older than 30 years; younger women may not be affected. In contrast to MOPP, the ABVD combination appears to spare female fertility." The biggest concerns for long-term effects or hazards are the chances of developing secondary malignancies and cardiovascular disease. The types of secondary malignancies one can develop are solid tumors, lymphoma, and leukemia. The longterm cardiovascular risks are coronary artery disease, pericarditis, valvular disease, and pancarditis. <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">1 || Hodgkin's disease is considered a curable form of cancer. It is extremely radiosensitive. Therefore, Radiation therapy plays an important role in the treatment of Hodgkin's disease. It is used to treat all involved and potentially involved lymph nodes. The goal is to sterilize all sites of disease.3 <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> In early stages( I to IIA) irradiation can effectively be used alone. Recently, patients with advanced disease are being treated with a radiation therapy and chemotherapy combined-modality program. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> - The radiation dose required to eradicate Hodgkin's disease in clinically involved nodes is approximately 36 to 44 Gy. - 25 to 36 Gy is the doses required for prophylactic treatment. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">3 <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> - The daily treatment fractions should be delivered in 1.5 to 1.8 Gy.
 * Radiation Side Effects: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Less than 5% of patients develop radiation pneumonitis within 6 to 12 weeks of completing mantle radiation treatments. The risk for developing this is realted to amount of lung that was irradiated, the total dose received and the dose per fraction. Most of the time people are just treated symptomatically but sometimes treatment with corticosteroids is necessary. "Radiation pericarditis after well-executed mantle therapy is seen in less than 5% of patients and can be managed with conservative medical treatment." Subclinical hypothyroidism develops in approximately one-half of patients with HD, manifested by an elevation of hte sensitive thyroid-stimulating hormone even with a normal thyroxine (T4) level." In this situations, thyroid replacement therapy is recommended. For 10%-15% of patients, herpes zoster occurs during treatment of within the first couple years after treatment. Approximately 10%-15% of patients develop Lhermitte's sign after mantle therapy, which usually spontaneously resolves after 2 to 6 months. Splenectomy patients can develop postsplenectomy sepsis which is caused by Streptococcus pneumoniae, meningococcus, and haemophilus strains. The chances of developing this can be reduced by immunizing against these organisms prior to surgery. Azoospermia in men can be caused by pelvic irradiation if proper precautions aren't taken to shield the testes. In addition, "MOPP or MOPP-like chemotherapy that includes alkylating agents and procarbazine causes sterility in most men." The ABVD regimens on the other hand, seem to spare male fertility. "Even with a proper oopherectomy and well-planned pelvic irradiation, the scattered dose of radiation may be sufficient to affect ovarian function and cause
 * Prognosis: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The histology of Hodgkin's has the least effect on the prognosis of a particular patient, whereas the stage of the disease has the greatest effect. The later the stage, the worse the prognosis. More males than females are diagnosed with Hodgkin's lymphoma, and the prognosis is slightly worse for males as well. Youth is a favorable prognostic factor, with younger patients (those in their teens to twenties) doing better than older patients, who cannot tolerate the aggressive treatment. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">7 ||
 * Treatments: || Surgery is used for the tissue biopsy needed for diagnosis. Staging laparotomy and splenectomy are rarely used anymore. 3 Female patients that are candidates for pelvic irradiation may undergo a mid-line or lateral oophoropexy.

- includes the cervical, submandibular, axillary, supraclavicular, infraclavicular, mediastinal, and hilar lymph nodes. - Used to treat the lymph node areas above the diaphragm. - The chin is extended and the superior border is at the lower mandible and mastoid tips. - Inferior border is at the insertion of the diaphragm (T9-T10). - The lateral borders should include the axillary nodes. 4 - Figures 1.1 and 1.2 are examples. Figure 1.1 AP Mantle Sim film with custom blocks Figure 1.2 PA Mantle Sim Field with custom blocks
 * AP/PA Mantle Field**

- Includes the retroperitoneal or periaortic, pelvic nodes, femoral nodes, the spleen or the splenic hilar nodes. 4 - Superior border of the Periaortic is approximately at mid T10. The exact border is determined from the gap from the mantle field. - Inferior border is L4-L5. See figure 1.3. - The field width is usually 9-10 cm wide. Blocks may be cut to include the spleen or splenic pedicle. - The superior border of the pelvic portion of the inverted Y is approximately L-5 (actual gap from Periaortic field). - Inferior border is 2cm below the ischial tuberosity (including the femoral nodes). - The lateral borders are 2cm beyond the pelvic inlet. 4 - Figure 1.3 is an example paraortic AP field with custom kidney blocks. - Figure 1.4 is a diagram example of a mantle field and a divided inverted Y field .4 Figure 1.3 Paraortic AP field.
 * AP/PA Inverted Y field **
 * -** This large field can be divided into abdominal and pelvic ports for sequential treatments.

. Figure 1.4 Superior field is a mantle. The inferior fields are a divided Paraortic and Pelvic inverted Y. 4

- Field shaping and custom blocks play an important role in protecting the lungs, spinal cord, larynx, heart, humeral and femoral heads, kidneys, gonads, and iliac crest bone marrow. 3 The custom blocks can be very heavy.

- This term is used when the patient is treated to all three fields including; mantle field, para-aortic field (with spleen or splenic pedicle), and pelvic field separately or in a single inverted Y. 3 -** Refers to the treatment of a mantle field followed by a para-aortic field. - Most widely used treatment for stage IA or IIA patients .3 - Figure 1.2 below shows guidelines for treatment of Hodgkin's in Adults. 3
 * Total nodal irradiation (TNI)**
 * Subtotal nodal irradiation (STNI)

Figure 1.2 Adult treatment guidlines. 3

- Studies show low dose radiation therapy and combined chemotherapy may be a better choice, to reduce late term side effects.3 - Attempts should be made to position breast tissue under the lung blocking. - Adolescent early-stage male patients may be considered for radiation therapy alone. - The risk of second malignant neoplasms, require careful planing and judgment. Precise placement of blocks can be used to shield thyroid gland in some patients. - Figure 1.3 shows the guidelines for treatment of pediatric Hodgkin's disease. 3
 * Special considerations for treating pediatric Hodgkin's patients include; **

Figure 1.3 Pediatric treatment guidelines. 3 || Spinal cord --4500 cGy Lung ---3000 cGy Thyroid 4500 cGy Parotid- -3200 cGy Heart -4500cGy kidneys -1500 cGy Liver --2500 cGy intestine -4500 cGy ovary -200-300 cGy Testis --- 100 cGy || References: <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 121%;">1. Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions. 2nd edition//. Philadelphia, PA: Lippincott Williams & Wilkins. 1999, 2002; 576-577,585-586. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 121%;">2. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 12pt;">Gunders on, LL & Tepper, JE. (Eds.) //<span style="font-family: 'Calibri','sans-serif';">Clinical Radiation Oncology //. 2nd edition. Philadelphia, PA: Elsevier, Churchill & Livingstone. 2007: 1690-1693. 3. Rubin P. //Clinical Oncology A multidisciplinary Approach for Physicians and Students. 8th Edition.//Philadelphia, PA : W.B. Saunders Company. 2001;305-312. 4. Dasher B, Wiggers N, Vann AM. //Portal Design in Radiation Therapy//. Columbia, SC : The R.L. Bryan Company; 69-74. 5. Washington C M, Leaver D. //Principles and Practice of Radiation Therapy//. Second Edition. St. Louis, Missouri: Mosby Inc. 2004; 80-81, 578, 594-595. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">6. Lenhard RE, Osteen RT, Gansler T. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta, GA: The American Cancer Society, Inc. 2001: 497-498. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;">7. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 2nd ed. St. Louis, MI: Mosby. 2004: 591-592. 8. Wikipedia. Hodgkin's Lymphona. Available at: [|http://en.wikipedia.org/wiki/Hodgkin's_lymphoma] . Accessed February 14, 2010.
 * TD5/5: || **Organ -TD5/5** 5