Lymphomas of the Head and Neck Follow-up

Otolaryngologists are required to perform regular nasopharyngeal laryngoscopy in patients whose initial presentation involved findings in the nasopharyngeal cavity, mouth, or sinuses.

In addition, otolaryngologists may be required to perform a biopsy when suspicious lesions are present in these areas. They may also need to perform biopsy for suspicious neck nodes during follow-up to obtain a histopathologic specimen to examine for recurrence.

For patients with HL anticipating mantle irradiation, abstinence from smoking is essential to minimize their risk of lung carcinoma.

In addition, patients who receive bleomycin are at risk for lung toxicity.

When possible, mantle irradiation should be avoided in people who smoke and in young women because of the risks of lung and breast cancer, respectively, as secondary neoplasia is the most common cause of long-term treatment-related mortality.

Because of the high cure rates for patients with lymphoma, particularly those with HL, the long-term adverse effects of therapy are important considerations and these effects have recently been realized in long-term follow-up of patients with HL. ^{[20, 21]} Mortality from causes other than HL overtakes HL deaths at 15 years after diagnosis, and because the median age at diagnosis is 44 years, most are treatment-related deaths. Deaths from second malignancies become the most important cause of death other than HL itself.

• The risk of leukemia is maximal at 5-10 years after treatment. Leukemia rarely occurs after the second decade. Although it is observed after irradiation alone, the relative risk is an order of magnitude less than the risk after therapy with alkylating agents.

  • The addition of involved-field irradiation increases the risk only marginally if at all, but extended-field irradiation with chemotherapy increases the risk from 2-3% to 6-9% at 10-15 years.

  • The risk of leukemia is linearly related to the total dose of alkylating agents. Repeated courses of drug, as in the treatment of relapses with the same amount of alkylating agent over 2 or more periods, may increase the risk 40-fold.

  • The risk of leukemia after ABVD is less than that after MOPP therapy.

• The risk of NHL is increased after treatment for HL, even in the first 5 years, and the cumulative risk is 4.1% after 20 years and levels off by the middle of the second decade after treatment.

  • The incidence of gastrointestinal involvement is high.

  • Increasing age at treatment of HL is correlated with an increasing risk of secondary NHL or leukemia.

• After patients are cured of HL, second neoplasms other than leukemia or NHL are the most common challenge in achieving a normal life span.

  • The risk of solid cancer continues well beyond the second decade, with no indication of when, if ever, it diminishes.

  • The 20-year cumulative risk of solid tumors is 13.1% compared with 8.1% for leukemia and NHL combined.

  • The major carcinogenic role is attributed to irradiation because approximately two thirds of the second solid tumors arise in or at the edge of treatment fields.

• The risks of other cancer may increase.

  • The risk of lung cancer increases 2- to 8-fold after radiotherapy or combined regimens containing alkylating agents.

  • The excess risk of breast carcinoma predominantly affects women undergoing irradiation before the age of 30 years. Breast carcinomas begin to appear at the end of the first decade after HL irradiation and continue at increased frequencies for at least 3 decades (longest observation period so far). Calculations in women with HL who were treated before the age of 20 years predict a 34% incidence of breast cancer at 25 years after irradiation.

  • The absolute risk of carcinomas of stomach, pancreas, and thyroid; sarcomas of the bone and soft tissue; and melanomas continues to increase in the third decade after treatment.

  • An increase in colorectal cancer has also been reported in pediatric patients who had HL.

• Cardiovascular complications of mantle irradiation are second only to new neoplasms as the most frequent cause of treatment-related mortality in patients with HL.

  • The relative risk of cardiac death is modest (2.2-3.1), but the absolute risk is high (9.3-28 cases per 10,000 patients per year), with a cumulative risk of cardiac mortality after 22 years of 23% for men and 8% for women.

  • Myocardial infarction accounts for more than two thirds of these deaths (15.5% of treated men and 3.5% of treated women at 22 y).

  • Refinement of irradiation techniques, such as the introduction of equal anterior and posterior fractions, reduced fraction size, and routine left ventricular and subcarinal blocking to limit doses to the entire cardiac silhouette, has led to a nearly one quarter reduction in the risk of radiation damage to the pericardium, myocardium, and heart valves. However, the number of deaths from myocardial infarction has not decreased.

Other complications of radiation therapy are hypothyroidism (after mantle irradiation), xerostomia, pharyngitis, fatigue, and weight loss.

• Pulmonary complications are radiation pneumonitis, which is severe in fewer than 5% of patients, and symptomatic pulmonary fibrosis, which occurs in fewer than 1% of patients.

• Para-aortic irradiation is rarely associated with clinically significant adverse effects.

• Pelvic irradiation induces acute, transient diarrhea and bladder irritation associated with urinary frequency.

• Long-term effects include a potential for long-term bone-marrow suppression and sterility.

Patients treated for NHL can have late relapses at 7-10 years.

• Patients receiving standard chemotherapy have an increased risk for acute nonlymphoblastic leukemia or other malignant neoplasms, such as melanoma, HL, lung cancer, brain tumors, renal cancer, and bladder cancer.

• In patients with NHL, the late effects of radiation therapy are similar to those of HL (as described above).

A study by Seland et al indicated that in patients with NHL treated with radiation of the head and neck, those with untreated hormone dysfunction are at greater risk of subsequently developing chronic fatigue. The study’s results also suggested that patients whose dysfunction has been treated with hormone substitution are at no greater risk of chronic fatigue than are patients with normal hormone status. The study included 98 NHL survivors who had been treated with radiation to the head and neck region, 29% of whom had chronic fatigue. ^[22]

A study by Chelius et al found that in patients with indolent NHL of the head and neck, toxicities tend to be minimal for treatment with either very low–dose radiation (4 Gy) or higher-dose radiation (>4 Gy, median dose in this study being 30 Gy). However, patients in the 4 Gy group had lower rates of toxicity, with, for example, early toxicity of the orbit having an incidence of 42%, versus 96% in the higher-dose patients. ^[23]

Common toxicity-related effects of chemotherapy are nausea and vomiting, marrow suppression, alopecia, mucositis, pneumonitis, and neuropathy. Delayed effects of chemotherapy can include a risk of premature menopause and infertility and a small risk of anthracycline-induced cardiac toxicity.

After autologous stem-cell transplantation, late, nonrelapse mortality is primarily due to chronic lung damage, infection, and secondary malignancies. Late pulmonary fibrosis occurs in up to 6% of patients, and late fatal infections occur in 1-2%. The incidence of leukemia in patients undergoing transplantation is similar to the incidence in those receiving conventional chemotherapy, but the risk of secondary solid tumors is higher than with chemotherapy alone.

In early stage HL, factors associated with adverse outcomes are large mediastinal involvement, age older than 40 years, B symptoms, involvement at multiple sites, high ESR, high beta2-microglobulin, mixed-cellularity and lymphocyte-depleted histologies, and treatment with involved-field radiation.

For advanced HL, the International Prognostic Factors Project for Advanced Hodgkin's Lymphoma identified seven adverse factors at diagnosis: initial hemoglobin level of less than 10.5 g/dL, albumin value less than 4 g/dL, stage IV disease, male sex, white blood cell count greater than 15,000 cells/mm³, absolute lymphocyte count of less than 600 cells/mm³, and age older than 45 years. Each of these factors decreases the 5-year progression-free survival rate by 7-8%.

In patients with aggressive B-cell NHL (eg, DLBCL), the prognosis depends on age (< 60 or >60 y), serum lactate dehydrogenase (LDH) levels, performance status, stage, and extranodal involvement. Response to treatment is also an important prognostic indicator.

A study by Teckie et al indicated that in patients with early stage extranodal marginal-zone lymphoma, those with lymphoma of the stomach or the head and neck have the highest likelihood of relapse-free survival following treatment with curative-intent radiation therapy alone. The study utilized the records of 490 patients (median follow-up 5.2 y) with stage IE or IIE marginal-zone lymphoma, located most frequently in the stomach, orbit, skin, breast, or nonthyroid head and neck. ^[24]

A study by Eismann et al indicated that following systemic therapy, image-guided intensity-modulated radiotherapy (IG-IMRT) offers some benefit over three-dimensional conventional radiotherapy (3DCRT), in patients with aggressive head and neck extranodal NHL. Patients who received IG-IMRT had an overall response rate of 85%, compared with 73% in individuals who underwent 3DCRT. Moreover, there were fewer acute or chronic adverse events associated with IG-IMRT. ^[25]

For patient education resources, see the Cancer and Tumors Center, as well as Brain Cancer and Cancer of the Mouth and Throat.