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Cancer Survivorship, a Unique and Growing Cohort in Medical Practice: Radiology Perspective

      Abstract

      The unique medical and psychologic burdens of cancer survivorship have only recently been recognized. This rapidly expanding cohort of patients will be seen increasingly by non-oncology physicians who must consider medical issues related to their cancer or its therapy for any presenting symptoms. Appropriate use of clinical imaging is essential for diagnosing treatment-related complications, recurrent tumor, or emergence of second primaries. This article will review clinical imaging in common medical problems uniquely found in cancer survivors.

      Keywords

      At least 2 of every 3 current patients with cancer will be alive 5 years after their diagnosis.
      • American Cancer Society
      Cancer Facts and Figures, 2009.
      • Ganz P.A.
      Survivorship: adult cancer survivors.
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      Long term survival rates of cancer patients achieved by end of the 20th century: a period analysis.
      • Miller K.D.
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      Medical issues in cancer survivors: a review.
      However, the medical “price” of cure or prolonged survival can be substantial, with a wide range of major and minor, long- and short-term complications. Overall, the cumulative risk of any chronic health condition in cancer survivors was 78% and a cumulative risk of 42% for severe, disabling, or life-threatening problems.
      • Oeffinger K.C.
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      • et al.
      Chronic health conditions in adult survivors of childhood cancer.
      Non-oncology practitioners can expect to encounter increasing numbers of cancer survivors and their unique set of medical risks, including treatment-related complications, tumor recurrence, and second primary cancer. Unfortunately, the prevalence and incidence of a broad range of complications remain largely unknown and will undoubtedly be dependent on the site and characteristics of the primary tumor and its therapy. Many reported long-term sequelae, such as fatigue, anxiety, and depression, may manifest in a range of physical symptoms.
      • Aziz N.M.
      Cancer survivorship research: state of knowledge, challenges, and opportunities.
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      Knowledge, ignorance and priorities for research in key areas of cancer survivorship: findings from a scoping review.
      Nevertheless, there are clearly a number of general, predictable medical issues in cancer survivors that can be expected to occur frequently. Appropriate application of clinical imaging is an essential part of the care in this cohort of patients.
      • Cancer survivors are a rapidly expanding cohort, and many patients are being seen by primary care physicians.
      • This cohort has unique medical problems that result from the disease process itself as well as treatment.
      • Radiology plays an important function in evaluating these patients. This article reviews clinical imaging in common medical problems uniquely found in cancer survivors and which modalities will be helpful in evaluating these patients in common clinical scenarios.
      We will review the radiologic manifestation of the common consequences of cancer and its therapy. There are 2 general sequelae:
      • Organ, tissue, or systemic damage related to therapy. Typically, this will include local scarring and inflammation due to surgery or radiation therapy. In addition, systemic therapy may cause inflammation, scarring, or necrosis in a broad range of target organs, including the lung, liver, kidneys, brain, and peripheral nerves.
      • Emergence of a new cancer site: This will most frequently represent late-recurrence of the initial treated tumor. However, second primary cancers may result from the same underlying germline mutation that produces the original tumor (eg, ovarian cancer in BRCCA1 mutations) or as a result of mutagenic effects of radiation or chemotherapy.

      Pulmonary

      Many chemotherapy agents can cause toxicity to the lungs. The effects on the lung can be acute, subacute, or chronic. Early-onset manifestations can present as infiltrates, pulmonary edema, and pleural effusions. Later-onset manifestations include lung fibrosis and pulmonary artery hypertension.
      • Torrisi J.M.
      • Schwartz L.H.
      • Gollub M.J.
      • Ginsberg M.S.
      • Bosl G.J.
      • Hricak H.
      CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity.
      Bleomycin is a common chemotherapy agent that can cause pneumonitis within 1 to 6 months after commencing therapy and interstitial fibrotic changes that can present months or years after treatment is completed (Figure 1).
      • Torrisi J.M.
      • Schwartz L.H.
      • Gollub M.J.
      • Ginsberg M.S.
      • Bosl G.J.
      • Hricak H.
      CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity.
      • Vahid B.
      • Marik P.E.
      Pulmonary complications of novel antineoplastic agents for solid tumors.
      Figure thumbnail gr1
      Figure 1(A) CT scan in patient with Hodgkin's lymphoma demonstrates normal lung parenchyma at time of diagnosis before initiation of chemotherapy. (B) After 3 months of therapy with regimen including bleomycin CT through the lung bases, new areas of ground glass opacities and thickening of the septa (arrows) are demonstrated, consistent with interstitial pneumonitis.
      Some of the newer molecularly targeted agents, such as gefitinib and imatinib, can cause pulmonary toxicity, ranging from acute pneumonitis to chronic fibrosis.
      • Vahid B.
      • Marik P.E.
      Pulmonary complications of novel antineoplastic agents for solid tumors.
      These toxicities typically present with dyspnea, cough, or shortness of breath and nonspecific laboratory values, such as elevated white blood cell count, elevated erythrocyte sedimentation rate, and elevated C-reactive protein levels.
      • Torrisi J.M.
      • Schwartz L.H.
      • Gollub M.J.
      • Ginsberg M.S.
      • Bosl G.J.
      • Hricak H.
      CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity.
      • Vahid B.
      • Marik P.E.
      Pulmonary complications of novel antineoplastic agents for solid tumors.
      Radiation therapy is a common treatment modality for lung and breast malignancy and can cause lung toxicity similar to chemotherapy, including pneumonitis and fibrosis (Figure 2). Because these symptoms are nonspecific and often overlap, more common causes must be ruled out, such as infection, pulmonary embolus, and edema. Clinical history, physical examination, and imaging modalities, if warranted, must be used integrally to discern a cause.
      Figure thumbnail gr2
      Figure 2A 70-year-old man with a history of right lung adenocarcinoma successfully treated with radiation therapy. (A) Axial CT image demonstrates traction bronchiectasis (arrow) and honeycombing (solid arrow), consistent with fibrotic changes from radiation. (B) Coronal image again demonstrates areas of traction bronchiectasis (arrow).
      Conventional radiographs are often the first modality ordered when evaluating a patient with chest symptoms. The chest radiograph exposes the patient to a low radiation dose compared with computed tomography (CT) and is lower in cost. The pattern and change between serial radiographs can help create a differential diagnosis.
      • Oh Y.W.
      • Effmann E.L.
      • Godwin J.
      Pulmonary infections in immunocompromised hosts: the importance of correlating the conventional radiologic appearance with the clinical setting.
      Chest radiographs are not as sensitive or specific for thoracic pathology but are a good starting point and can indicate a need for additional imaging depending on the clinical history and findings. The American College of Radiology recommends chest radiography as the initial study for the evaluation of acute respiratory illness in immunocompromised patients.
      • Heitkamp D.
      • Mohammed T.
      • Kirsch J.
      • et al.
      ACR appropriateness criteria-Acute respiratory illness in immunocompromised patients.
      Chest CT is a more sensitive and specific modality for detecting subtle thoracic abnormalities but also carries a substantially higher ionizing radiation dose when compared with conventional radiography.
      • Tomiyama N.
      • Muller N.L.
      • Johkoh T.
      • et al.
      Acute parenchymal lung disease in immunocompetent patients: diagnostic accuracy of high-resolution CT.
      CT usually permits distinction between infectious and noninfectious causes.
      • Tomiyama N.
      • Muller N.L.
      • Johkoh T.
      • et al.
      Acute parenchymal lung disease in immunocompetent patients: diagnostic accuracy of high-resolution CT.
      The current gold standard in evaluation for pulmonary embolism is contrast-enhanced CT pulmonary angiography (Figure 3), which is sensitive and specific for detection of pulmonary embolism
      • Coche E.
      • Verschuren F.
      • Keyeux A.
      • et al.
      Diagnosis of acute pulmonary embolism in outpatients: comparison of thin collimation multi-detector row spiral CT and planar ventilation-perfusion scintigraphy.
      when compared with other modalities. Because intravenous contrast is required, the patient's renal function must be determined before the study. CT also has better resolution than plain film or magnetic resonance imaging (MRI) and is more sensitive for the detection of smaller nodules that can be seen in infection, as well as recurrent disease.
      Figure thumbnail gr3
      Figure 3Patient with sarcoma with acute shortness of breath. (A) Axial image from CT scan demonstrates a filling defect within the right main pulmonary artery (solid arrow), consistent with pulmonary embolism. (B) Coronal image demonstrates filling defect within the right main and lower lobar pulmonary arteries (solid arrow).
      Advances in technology have increased the utility of MRI of the lung. MRI can be considered as a nonionizing radiation alternative in younger patients, pregnant patients, and patients with contrast allergies
      • Biederer J.
      • Mirsadraee S.
      • Beer M.
      • et al.
      MRI of the lung (3/3)-current applications and future perspectives.
      CT demonstrates better resolution of small nodules, but MRI can detect nodules approximately 3 to 4 mm in size.
      • Biederer J.
      • Hintze C.
      • Fabel M.
      MRI of pulmonary nodules: technique and diagnostic values.
      MRI delivers better soft tissue contrast and has good sensitivity and specificity in evaluating lung disease.
      • Montella S.
      • Maglione M.
      • Bruzzese D.
      • et al.
      Magnetic resonance imaging is accurate and reliable method to evaluate non-cystic fibrosis paediatric lung disease.
      MRI also can be considered for evaluation of pulmonary embolism in patients who have contraindications to receiving CT pulmonary angiography (ie, contrast allergy or renal insufficiency).
      • Kalb B.
      • Sharma P.
      • Tigges S.
      • et al.
      MR imaging of pulmonary embolism: diagnostic accuracy of contrast enhanced 3D MR, pulmonary angiography, contrast enhanced low-flip angle 3d GRE and non-enhanced free-induction FISP sequences.
      However, MRI is a more expensive modality when compared with conventional radiography and CT. In addition, chest MRI may not be available at every institution or imaging center, and differences in quality of the study often depend on that institution's experience.

      Genitourinary

      The genitourinary system is subject to complications from cancer treatment ranging from toxicity of chemotherapy to post-surgical or radiation-induced scarring or obstruction. Renal failure in patients with cancer is often multifactorial.
      • Humphreys B.D.
      • Soiffer R.J.
      • Magee C.C.
      Renal failure associated with cancer and its treatment: an update.
      Antineoplastic agents, such as mitomycin C and gemcitabine, have been associated with thrombotic microangiopathy syndromes, which can lead to renal failure. Bisphosphonates, which are often used to treat osteolytic metastases and hypercalcemia of malignancy, are excreted by the kidneys, resulting in dose-dependent nephrotoxicity.
      • Torrisi J.M.
      • Schwartz L.H.
      • Gollub M.J.
      • Ginsberg M.S.
      • Bosl G.J.
      • Hricak H.
      CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity.
      • Vahid B.
      • Marik P.E.
      Pulmonary complications of novel antineoplastic agents for solid tumors.
      Allogeneic hematopoietic cell transplant is a common technique used in hematology and oncology and has been associated with chronic renal failure in certain subsets of patients with hypertension.
      • Kang S.H.
      • Park H.S.
      • Sun I.O.
      • et al.
      Changes in renal function in long term survivors of allogeneic hematopoietic stem cell transplantation.
      In rare cases, radiation therapy can have effects on the renal artery causing renal artery stenosis and refractory hypertension, which presents as a late finding.
      • Tacconi S.
      • Bieri S.
      Renal artery stenosis after radiotherapy for Ewing's sarcoma.
      Ultrasound is a good screening modality for evaluating patients with renal insufficiency. It is widely available and noninvasive, and delivers no ionizing radiation. Evaluation for hydronephrosis can be quickly and easily made. Chronic renal disease can present as hyperechoic small kidneys with cortical thinning (Figure 4). Ultrasound has limited sensitivity when compared with CT for detecting calculi and is poor at depicting calculi 3 mm or less, but it has a relatively high specificity and high positive predictive value.
      • Fowler K.A.
      • Locken J.A.
      • Duchesne J.H.
      • Williamson M.R.
      US for detecting renal calculi with non-enhanced CT as reference standard.
      Contrast-enhanced CT and MRI are more sensitive for detecting cortical masses and demonstrate better evaluation of surrounding structures.
      Figure thumbnail gr4
      Figure 4Ultrasound images from 3 different oncology patients with a history of renal failure. (A) Sagittal ultrasound image demonstrates echogenic renal cortex (arrows) brighter than the adjacent liver (star), which can be seen in medical renal disease. The normal kidney should be less bright or equal in echogenicity to the liver. (B) Sagittal image of the right kidney in a separate patient demonstrates a bright focus with shadowing present (arrow) in the right lower pole consistent with a renal calculus. (C) Sagittal image of the left kidney in another patient demonstrates connected anechoic spaces (stars) representing dilated calyces and renal pelvis consistent with hydronephrosis. INF = inferior; LAT = lateral; LLD = left lateral decubitus; LT = left; RT = right; SAG = sagittal.
      CT is an excellent modality for evaluating postsurgical complications, renal calculi, and other causes of abdominal pain. Multiplanar reformatted images are an excellent way to demonstrate anatomy and pathology. CT is widely available and has a fast acquisition time. However, CT uses radiation, and the use of iodinated contrast may be limited in patients with renal insufficiency.
      In patients with renal insufficiency who cannot receive intravenous iodinated CT contrast, MRI can be considered with or without contrast. MRI does not use ionizing radiation or iodinated contrast, allows for 3-dimensional reformats in any plane, and has better contrast delineation when compared with CT. MRI can demonstrate postsurgical complications, such as seroma, lymphoceles, and strictures. MRI allows improved evaluation of other surrounding structures when compared with ultrasound but is limited in sensitivity for detecting renal calculi when compared with CT.
      • Garcia-Valtuille R.
      • Garcia-Valtuille A.
      • Abascal F.
      • Cerezal L.
      • Arguello M.
      Magnetic resonance urography: a pictorial overview.

      Musculoskeletal

      Cancer therapy can have varied effects on the musculoskeletal system. Hormonal therapy, bisphosphonates, corticosteroids, radiation treatments, and entities such as graft-versus-host disease increase the risk for osteopenia and avascular necrosis. Complications can occur 3 to 5 years after receiving treatment.
      • Newland A.M.
      • Lawson A.P.
      • Adams V.R.
      Complications associated with treatment of malignancies: a focus on avascular necrosis of the bone.
      Avascular necrosis (Figure 5) is associated with death of bone and marrow due to compromise of blood flow and vasculature.
      • Newland A.M.
      • Lawson A.P.
      • Adams V.R.
      Complications associated with treatment of malignancies: a focus on avascular necrosis of the bone.
      • Cook A.M.
      • Dzik-Jurasz A.S.
      • Padhani A.R.
      • Norman A.
      • Huddart R.A.
      The prevalence of avascular necrosis in patients with chemotherapy for testicular tumours.
      Patients with cancer are at higher risk because of the medications, radiation treatment, and malignancy itself. Avascular necrosis may present in 1% to 10% of patients receiving chemotherapy.
      • Cook A.M.
      • Dzik-Jurasz A.S.
      • Padhani A.R.
      • Norman A.
      • Huddart R.A.
      The prevalence of avascular necrosis in patients with chemotherapy for testicular tumours.
      Presenting symptoms include pain, swelling, or limited mobility of the joints and may be difficult to distinguish clinically from infection and new metastatic disease. Radiographs are a good first-line test, are inexpensive to evaluate for suspicion of avascular necrosis, and should be obtained as the initial study.
      • Cook A.M.
      • Dzik-Jurasz A.S.
      • Padhani A.R.
      • Norman A.
      • Huddart R.A.
      The prevalence of avascular necrosis in patients with chemotherapy for testicular tumours.
      MRI is a more sensitive and specific modality for detecting changes of avascular necrosis and detects changes earlier than plain film or CT. MRI is often considered when there are equivocal findings on plain film or for screening other joints, such as the opposite hip when looking for areas of asymptomatic avascular necrosis. MRI has increased cost compared with plain films. Radionuclide bone scanning has been used for detection of early avascular necrosis before the advent of MRI and is more sensitive than conventional radiography but less sensitive than MRI.
      • Love C.
      • Din A.S.
      • Tomas M.B.
      • Kalapparambath T.P.
      • Palestro C.J.
      Radionuclide bone imaging: an illustrative review.
      Figure thumbnail gr5
      Figure 5Images from childhood cancer survivor with right hip pain. (A) Plain film of the right hip demonstrates sclerosis of the right femoral head (arrow), consistent with avascular necrosis. (B) Axial MRI demonstrates bright abnormal signal within the femoral head (arrows), consistent with marrow changes that can be seen with avascular necrosis. Increased signal is seen adjacent to the femoral head (arrowhead), consistent with a small hip effusion. (C) Coronal MRI again demonstrated bright abnormal signal in the right femoral head (arrows). Low signal is identified within the femoral head (star) correlating with sclerosis seen on plain film.
      Osteopenia and osteoporosis are common in cancer survivors for a multitude of factors, including treatment and age. Bone densitometry is a sensitive modality for measuring bone mass and predicting fracture risk.
      • Sweeney A.T.
      • Malabanan A.O.
      • Blake M.A.
      • et al.
      Bone mineral density assessment: comparison of dual-energy x-ray absorptiometry measurements at the calcaneus, spine and hip.
      Dual-energy X-ray absorptiometry is the gold standard for evaluating bone mass density with relatively low radiation exposure. Quantitative CT determines bone density by comparing with a series of phantoms. Quantitative CT provides a true volumetric measurement of bone and appears as precise as dual-energy X-ray absorptiometry but has increased radiation exposure.

      Richmond B, Daffner R, Weissman B, et al. ACR appropriateness criteria–osteoporosis and bone mineral density. 2010.

      Gastrointestinal

      Cancer therapy can have short- and long-term sequelae in the gastrointestinal tract. Because of rapid turnover of cells within the mucosa, the gastrointestinal tract is susceptible to radiation therapy, which can cause inflammation acutely and lead to fibrosis and vasculitis chronically. Chronic radiation effects in the bowel were reported in 0.5% to 16.9% of patients receiving radiation for abdominal and pelvic malignancies.
      • Sher M.E.
      • Bauer J.
      Radiation-induced enteropathy.
      Surgical and radiation changes can cause problems with motility, malabsorption, and obstruction from adhesions and fistula. The effects of chemotherapeutic agents include hepatitis and veno-occlusive disease, and can lead to liver fibrosis chronically.
      • King P.D.
      • Perry M.C.
      Hepatotoxicity of chemotherapy.
      In the immunocompromised state, patients are more susceptible to infections such as Clostridium difficile (Figure 6).
      Figure thumbnail gr6
      Figure 6Immunosuppressed patient with cancer with abdominal pain. Coronal CT images (A, B) demonstrate diffuse wall thickening throughout the entire colon (arrows), consistent with Clostridium difficile colitis.
      Graft-versus-host disease can be a complication of stem cell transplantation, which can affect many organ systems. Graft-versus-host disease occurs from the donor immune system attacking the recipient tissues and can occur in acute and chronic forms.
      • Sung A.
      • Chao N.
      Concise review: acute graft-versus-host disease: immunobiology, prevention and treatment.
      This disease can affect any part of the gastrointestinal tract from the esophagus to rectum. Symptoms can include abdominal pain, nausea, vomiting, and liver dysfunction. Imaging findings are nonspecific, with the primary bowel findings being bowel wall thickening and abnormal mucosal enhancement.
      • Mahgerefteh S.Y.
      • Sosna J.
      • Bogot N.
      • Shapira M.Y.
      • Pappo O.
      • Bloom A.I.
      Radiologic imaging and intervention for gastrointestinal and hepatic complications of hematopoietic stem cell transplantation.
      Hepatic graft-versus-host disease is primarily a disease of the biliary system and may manifest as hepatitis or cirrhosis. Patients who are recipients of autologous or allogeneic stem cell transplantation may develop secondary iron overload that can manifest as liver failure.
      • Boll D.
      • Merkle E.
      Diffuse liver disease: strategies for hepatic CT and MR imaging.
      Plain films often are ordered in the evaluation of patients presenting with abdominal pain but have only moderate sensitivity for detecting small bowel obstruction and low sensitivity for sources of abdominal pain or fever.
      • Ahn S.H.
      • Mayo-Smith W.W.
      • Murphy B.L.
      • Reinert S.E.
      • Cronan J.J.
      Acute nontraumatic abdominal pain in adult patients: abdominal radiography compared with CT evaluation.
      Abdominal films deliver less ionizing radiation than CT and are lower cost (Figure 7).
      Figure thumbnail gr7
      Figure 7Oncology patient who presented with nausea and vomiting. (A) Portable view of the abdomen demonstrates dilated loops of bowel centrally (arrows) suspicious of small bowel obstruction. Incidental note is made of consolidation in the right lower lobe, consistent with pneumonia (arrowhead). (B) CT coronal image from the same patient demonstrates dilated loops of small bowel (arrows), consistent with small bowel obstruction.
      Fluoroscopy is used to visualize real-time motion of internal fluids, structures, or devices.
      • Pickhardt P.
      • Bhalla S.
      • Balfe D.M.
      Acquired gastrointestinal fistulas: classification, etiologies, and imaging evaluation.
      Fluoroscopy allows for real-time visualization and can be helpful in evaluating for postsurgical complications, such as leak or fistulas. CT is a mainstay of evaluating abdominal pain in patients. CT is accurate for evaluating small bowel obstruction,
      • Boudiaf M.
      • Soyer P.
      • Terem C.
      • Pelage J.P.
      • Maissiat E.
      • Rymer R.
      CT evaluation of small bowel obstruction.
      infection, and other causes. CT evaluates adjacent structures and gives more information than conventional radiography, such as fluoroscopy or plain films. More invasive techniques such as CT enteroclysis, which involves intubating the small bowel, can give more detailed evaluation for small bowel abnormalities and low-grade obstruction.
      • Walsh D.
      • Bender G.
      • Timmons H.
      Comparison of computed tomography-enteroclysis and traditional computed tomography in the setting of suspected partial small bowel obstruction.
      CT can be used to evaluate morphologic characteristics of the liver
      • Elsayes K.
      • Leyendecker J.
      • Menias C.
      • et al.
      MRI characterization of 124 CT indeterminate focal hepatic lesions: evaluation of clinical utility.
      and look for recurrent or metastatic disease. Contrast-enhanced CT allows for evaluation of the vasculature. CT exposes the patient to radiation, and if multiphase imaging is needed this increases the radiation dose.
      MRI gives more soft tissue contrast of structures and the ability to display dynamic information, and lacks ionizing radiation when compared with CT.
      • Taouli B.
      • Ehman R.
      • Reeder S.B.
      Advanced MRI methods for assessment of chronic liver disease.
      MRI can evaluate acute or chronic changes of bowel, including stricture or fistulous connections.
      • Fidler J.
      • Guimaraes L.
      • Einstein D.
      MR imaging of the small bowel.
      MRI has been used to evaluate acute and chronic changes of the liver.
      • Taouli B.
      • Ehman R.
      • Reeder S.B.
      Advanced MRI methods for assessment of chronic liver disease.
      Techniques such as MR elastography have been used to evaluate hepatic fibrosis.
      • Taouli B.
      • Ehman R.
      • Reeder S.B.
      Advanced MRI methods for assessment of chronic liver disease.
      It is a more sensitive and specific modality for characterizing liver lesions,
      • Elsayes K.
      • Leyendecker J.
      • Menias C.
      • et al.
      MRI characterization of 124 CT indeterminate focal hepatic lesions: evaluation of clinical utility.
      which is helpful for surveillance. MRI is more expensive than CT but can often give a more definitive answer, which may preclude more tests (eg, biopsy or additional imaging), thus saving cost.
      Ultrasound is a widely available noninvasive imaging method that does not use ionizing radiation. Ultrasound is not as sensitive for detection of bowel or liver abnormalities when compared with CT and MRI.
      • Ledermann H.
      • Borner N.
      • Strunk H.
      • Bongartz G.
      • Zollikofer C.
      • Stuckmann G.
      Bowel wall thickening on transabdominal sonography.
      Doppler ultrasound findings along with clinical information can suggest the development of veno-occlusive disease and are used for monitoring.
      • Sung A.
      • Chao N.
      Concise review: acute graft-versus-host disease: immunobiology, prevention and treatment.

      Monitoring for Recurrence

      Imaging guidelines have been established by different groups specific for certain malignancies for monitoring recurrent disease. Imaging and laboratory tests are used to screen for recurrent disease. Cancer survivors are at increased risk for secondary malignancies that are due to factors such as genetic predisposition and prior treatments with radiation and chemotherapy. Positron emission tomography (PET) is a diagnostic imaging technique that allows for the evaluation of physiologic activity within tissues and malignancy.
      • Kostakoglu L.
      • Agress Jr., H.
      • Goldsmith S.J.
      Clinical role of FDG PET in evaluation of cancer patients.
      PET-CT provides fused images that give the added ability to better localize regions of abnormal metabolism. PET-CT is extensively used for evaluating recurrent disease and has the ability to scan the whole body.
      • Israel O.
      • Kuten A.
      Early detection of cancer recurrence: 18f-FDG PET/CT can make a difference in diagnosis and patient care.
      Cancer-related abnormalities often show abnormal metabolism before imaging changes are present.
      • Israel O.
      • Kuten A.
      Early detection of cancer recurrence: 18f-FDG PET/CT can make a difference in diagnosis and patient care.
      The modality is used to evaluate response to treatment. It has the advantage of monitoring physiologic activity in postsurgical and post-treatment areas that may look abnormal from scarring or postsurgical changes on CT imaging alone. PET-CT has higher sensitivity for detecting recurrent disease for some malignancies when compared with conventional imaging alone.
      • Israel O.
      • Kuten A.
      Early detection of cancer recurrence: 18f-FDG PET/CT can make a difference in diagnosis and patient care.
      • Zimny M.
      • Siggelkow W.
      • Schroder W.
      • et al.
      2-Flourine 18-flouro-2-deoxy-d-glucose positron emission tomography in the diagnosis of recurrent ovarian cancer.
      • Metser U.
      • You J.
      • Mcsweeney S.
      • Freeman M.
      • Hendler A.
      Assessment of tumor recurrence in patients with colorectal cancer and elevated carcinoembryonic antigen level: FDG PET/CT versus contrast enhanced 64 MDCT of the chest and abdomen.
      • Son H.
      • Kositwattanarerk A.
      • Hayes M.P.
      • et al.
      PET/CT evaluation of cervical cancer: spectrum of disease.
      Contrast-enhanced CT still remains the most common modality used for screening and evaluating recurrent disease. CT has benefits of rapid acquisition times, wide availability, and high resolution.
      • Pannu H.K.
      • Corl F.M.
      • Fishman E.K.
      CT evaluation of cervical cancer: spectrum of disease.
      CT produces ionizing radiation, which has to be considered because these patients will likely receive many studies over their remaining life span.
      MRI has had increasing use in restaging and monitoring for recurrent disease because of advances in technology and more widespread availability. MRI does not produce ionizing radiation and can be used in younger patients and those with allergies to iodinated contrast (Figure 8). MRI is useful in imaging the pelvis and more sensitive than PET/CT and CT for detecting local recurrence and peritoneal lesions from pelvic malignancies, such as ovarian cancer.
      • Kim C.K.
      • Park B.K.
      • Choi J.Y.
      • Kim B.G.
      • Han H.
      Detection of recurrent ovarian cancer at MRI: comparison with integrated PET/CT.
      Figure thumbnail gr8
      Figure 8Patient with breast cancer who received remote radiation for breast cancer and developed left shoulder pain. (A) Axial CT image demonstrates sclerosis and expansion of the left clavicle with osseous matrix (arrow), consistent with secondary osteosarcoma. (B) Coronal pre-contrast T1-weighted MRI demonstrates a soft tissue mass involving the left clavicle. (C) Coronal post-contrast T1-weighted MRI demonstrates avid enhancement of patient's secondary osteosarcoma (arrowhead).
      Because of genetic factors, chemotherapy, and increased radiation exposure from therapy and imaging, cancer survivors are at increased risk of developing secondary malignancies.
      • Neglia J.
      • Friedman D.L.
      • Yasui Y.
      • et al.
      Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.
      • Meadows A.T.
      • Baum E.
      • Fossati-Bellani F.
      • et al.
      Second malignant neoplasms in children: an update from the Late Effects Study Group.
      Bone and soft tissue sarcomas are the most common secondary malignancies seen after radiation therapy. Leukemia can occur after treatment with chemotherapy. An increased incidence of solid tumors, such as thyroid cancer and secondary leukemia or lymphoma, has been found in patients with Hodgkin's lymphoma, who often receive combined therapy with chemotherapy and radiation.
      • Rheingold S.
      • Neugut A.
      • Meadows A.
      Secondary cancers: incidence, risk factors and management.
      Early diagnosis of secondary malignancy can lead to successful treatment. Adhering to imaging policies to limit ionizing radiation doses to as low as reasonably achievable
      • Meadows A.T.
      • Baum E.
      • Fossati-Bellani F.
      • et al.
      Second malignant neoplasms in children: an update from the Late Effects Study Group.
      will lower the cumulative dose a patient receives and decrease the risk of genetic mutations and cancer.

      Conclusions

      With the increasing number of cancer survivors, general practitioners can expect to encounter more oncologic patients in their practice. Because of previous or ongoing treatments, these patients have a high risk of short- and long-term sequelae that need to be considered, as well as common causes for any presenting symptoms. Cancer survivors also must be monitored for recurrence and are at increased risk for secondary malignancies. In conjunction with physical examination and laboratory values, imaging plays a vital part in the evaluation of cancer survivors for oncologic and non-oncologic issues. Conventional radiography is often a good starting point for evaluation of pulmonary symptoms and musculoskeletal issues because of low cost and low radiation dose. Plain films are less sensitive and specific than cross-sectional imaging. CT is an important modality for evaluation because of its widespread availability, high resolution, and fast acquisition time. However, CT also imparts an increased radiation dose, and efforts should be made to use imaging strategies with radiation doses as low as reasonably achievable, especially in younger patients. Iodinated contrast allergies and renal dysfunction must be considered if ordering contrast-enhanced CT. Because of advances in technology and increasing availability, MRI has had an increasing role in evaluating patients. MRI produces no ionizing radiation and has better soft-tissue contrast than CT and can be considered in young patients and patients with iodinated contrast allergy. Ultrasound is another option that produces no ionizing radiation, is portable, and is relatively low cost when compared with other cross-sectional imaging. Ultrasound overall is less sensitive for many processes when compared with MRI and CT. Ultrasound is heavily operator dependent, which means the quality of study may vary from place to place depending on experience and technique (Table). CT and PET CT are the mainstays for monitoring for recurrent disease.
      TableSummary of Some of the Available Imaging Modalities for Common Diagnoses in Oncologic Patients
      Symptom/SignPotential Cancer-related CauseImaging Options/Strategy
      DyspneaParenchymal fibrosis/inflammation

      Pleural effusion

      Recurrent tumor

      Cardiac failure

      Pulmonary embolus
      Plain film followed by CT with or without contrast as needed

      MRI of the chest may be considered in patients with iodinated contrast allergy or pregnant patients.
      Abdominal painBowel obstruction due to adhesions or tumor

      Recurrent tumor

      Ureteral/biliary obstruction

      Graft-versus-host

      Arterial or venous thrombosis

      Fistulous connection or leak
      Plain film, CT

      Fluoroscopy can be used for evaluation of leaks and fistulas.
      Renal failureRenal fibrosis

      Renal vein thrombosis

      Ureteral obstruction from calculi, fibrosis, or tumor

      Arterial insufficiency
      US/MRI/CT
      Hip painAVN

      Recurrent tumor

      Insufficiency fracture
      Plain film; MRI and CT for further characterization as needed
      Limb weakness/painMetastasis

      Deep venous thrombosis

      Fracture, pathologic, or insufficiency
      Plain film can be considered for first-line evaluation, especially if fracture is a concern.

      US if suspicion of DVT

      MRI/CT/nuclear medicine study can be used to evaluate for metastasis.
      Monitoring for recurrenceCT

      PET/CT

      MRI
      AVN = avascular necrosis; CT = computed tomography; DVT = deep vein thrombosis; MRI = magnetic resonance imaging; PET = positron emission tomography; US = ultrasound.

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      Linked Article

      • Thyroid Cancer in Cancer Survivors: The Role of Ultrasound and the Need for Committed Specialists
        The American Journal of MedicineVol. 127Issue 4
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          In their interesting review, Rose et al1 focus on the appropriate use of clinical imaging for diagnosing treatment-related complications, recurrent tumor, or emergence of second primaries in cancer survivors, which may result from mutagenic effects of radiation. We completely agree with the authors' conclusion, which suggests that survivors need to be considered for their higher risk of long-term sequelae, including second malignancies, and that general practitioners can rely on imaging in conjunction with physical examination and laboratory values.
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