Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report.

BACKGROUND: Although lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature. CASE PRESENTATION: A 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient's diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20). CONCLUSIONS: To the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.

Genomic characteristics and immune landscape of super multiple primary lung cancer.

BACKGROUND: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as 'super MPLC'. METHODS: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. FINDINGS: We report the genomic alteration landscape of super MPLC. EGFR, RBM10 and TP53 mutation and TERT amplification are important molecular events in the evolution of super MPLC. We propose the conception of early intrapulmonary metastasis, which exhibits different clinical features from conventional metastasis. The IHC analyses of PD-L1 and CD8 reveal a less inflamed microenvironment of super MPLC than that of traditional non-small cell lung cancer (NSCLC). We identify the potentially susceptible germline mutations for super MPLC. INTERPRETATION: Our study depicts the genomic characteristics and immune landscape, providing insights into the pathogenesis and possible therapeutic guidance of super MPLC. FUNDING: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

OBJECTIVE: Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. METHODS: From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. RESULTS: During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. CONCLUSIONS: Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

[Synchronous association of two primary lung tumors: a case report]. / Association synchrone de deux tumeurs pulmonaires primitives: à propos d'un cas.

Synchronous multiple primary lung tumors are a relatively rare entity with an increasing incidence in recent years due to the development of thoracic imaging and immunohistochemical techniques. The second lesion is considered in most cases as a secondary location, which partly explains the decrease in the incidence of this entity. We report the observation of a 74-year-old patient with two synchronous primary lung tumors, an adenocarcinoma and an epidermoid carcinoma. Through this clinical observation, we highlight the difficulty of diagnosing synchronous tumors and the major interest of new imaging modalities and immunohistochemical techniques for the optimal management of these tumors.

Synchronous Tumour: A Rare Case Report.

The occurrence of synchronous tumors is rare and there have been only a few reported cases. In this particular report, a 30-year-old female presented with abnormal heaviness and anorexia for one month. The case involved the presence of two simultaneous tumors: an immature teratoma in the ovary and a carcinoid tumor in the appendix. This case was complex and presented challenges for diagnosis and treatment. Although synchronous tumors are uncommon, they should be considered as a possibility in the differential diagnosis. Physicians may encounter difficulties in both clinical and histopathological diagnosis when dealing with such cases.

Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer.

Importance: The incidence of early-onset colorectal cancer (CRC) (age, <50 years) continues to increase globally within high-income countries. Objective: To examine and compare rates of synchronous neoplasia found in patients at colonoscopic diagnosis of early-onset CRC with rates found at diagnosis of average-onset CRC. Design, Setting, and Participants: In this multisite retrospective and cross-sectional study conducted at Mayo Clinic sites and in the Mayo Clinic Health System from January 1, 2012, to December 31, 2022, 150 randomly selected patients with early-onset CRC were identified from the electronic health record and matched with 150 patients with average-onset CRC based on sex and colonoscopic indication. Patients with known hereditary syndromes, past history of CRC, or inflammatory bowel disease were excluded. Main Outcomes and Measures: Colonoscopic findings (polyp size, number, site) and related histopathologic findings (adenoma, advanced adenoma, sessile serrated polyp) were analyzed in association with cancer clinicopathologic features and molecular data (mismatch repair status, KRAS, and BRAFV600E). Results: Among 300 patients (156 men [52%]), the median age at diagnosis was 43 years (IQR, 39-47 years) for those with early-onset CRC and 67 years (IQR, 57-76) for those with average-onset CRC. Overall, 85% of patients were symptomatic at CRC diagnosis. Cancer stage, grade, molecular features, body mass index, and family history did not differ significantly between these groups. Among patients with colon cancer, the overall prevalence of synchronous neoplasia was similar, yet advanced adenomas were 3 times more frequent in those with early-onset vs average-onset cancers (31 of 75 [41%] vs 10 of 75 [13%]; P < .001). This difference was not associated with cancer stage or primary location. Among patients with rectal cancer, nonadvanced adenomas were less frequent among the early-onset group than the average-onset group (21 of 75 [28%] vs 36 of 75 [48%]), and although the prevalence of advanced adenomas was similar (11 of 75 [15%] vs 14 of 75 [19%]), they were more commonly located in the rectum (early onset, 5 of 11 [45%] vs average onset, 1 of 14 [7%]). Patients with early-onset cancer of the colon were significantly more likely than those with early-onset cancer of the rectum to have a synchronous advanced adenoma (31 of 75 [41%] vs 11 of 75 [15%]; P < .001). Conclusions and Relevance: In this cross-sectional study, synchronous advanced adenomas were more commonly found in patients with early-onset colon cancer compared with average-onset colon cancer, and they were distributed throughout the colon. In contrast, advanced adenomas were not increased in patients with rectal cancer and, when detected, were predominantly located in the rectum.

Detection of collision metastases.

Cancer is a cause of high morbidity and mortality. It is not uncommon for a patient to have more than one primary tumour. This review summarises the knowledge of collision tumours which are defined as two adjacent neoplasms in the same organ, while a collision metastasis is the rare occurrence of two different primary cancers metastasising to the same anatomical site. Identification of collision metastasis is a diagnostic challenge and relies on histopathological examination. As it might have profound impact on prognosis and treatment decisions, it is important to create awareness among both pathologists and clinicians of this phenomenon.

Multiple Rare Primary Malignancies: A Mixed Squamous Neuroendocrine Adenocarcinoma of the Cervix, Metastasized Carcinosarcoma and Extramammary Vulvar Paget's Disease Case Report.

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget's disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget's disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team.

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer.

BACKGROUND: To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment. METHODS: Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups. RESULTS: Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups. CONCLUSION: Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.

Synchronous Second Primary Cancers of Hypopharyngeal Carcinoma in the Image-Enhanced Endoscopy Era.

OBJECTIVES: To explore the prevalence of hypopharyngeal carcinoma (HPC) with synchronous second primary malignancies (Syn-SPMs), their impact on clinical outcomes, and associated risk factors in the image-enhanced endoscopy era. MATERIALS AND METHODS: We retrospectively analyzed 673 patients newly diagnosed with HPC at our cancer center between 2009 and 2019. The patients were divided into three groups: (a) no second primary malignancies (N-SPMs, n = 533); (b) synchronous carcinoma in situ (Syn-Tis, n = 60); (c) synchronous invasive tumors (Syn-invasive, n = 80). Propensity score matching was conducted to balance the N-SPMs and Syn-invasive groups at a 3:1 ratio. RESULTS: Most (96.1%) underwent pretreatment esophagogastroduodenoscopy evaluation with image-enhanced endoscopy. The incidence rates were: Syn-SPMs, 20.8%; Syn-Tis, 8.9%; Syn-invasive, 11.9%. At a median follow-up of 66.7 months, the Syn-Tis and N-SPMs groups had a similar 5-year overall survival (OS; 45.6% vs. 44.5%; hazard ratio [HR], 0.956; 95% confidence interval [CI], 0.660-1.385; p = 0.806). Compared to the N-SPMs group, the Syn-invasive group had poorer 5-year OS (27.0% vs. 52.9%; HR, 2.059; 95% CI, 1.494-2.839; p < 0.001). Alcohol consumption was significantly associated with Syn-SPMs occurrence (odds ratio, 2.055, 2.414, and 3.807 for light, intermediate, and heavy drinkers, respectively). CONCLUSION: The prevalence of Syn-SPMs among patients with HPC was high. Syn-invasive SPMs decreased the survival of patients with HPC. Routine screening with image-enhanced endoscopy should be recommended to detect early-stage SPMs, especially for heavy alcohol drinkers. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1906-1913, 2023.

Multiple malignant primary tumors (non-head and neck): Contemplation needed.

BACKGROUND: The incidence of multiple malignant primary tumors (MMPT) is increasing which needs attention. Hence, we undertook this study to analyze clinico-demographic details and treatment outcomes in patients with non-head and neck MMPT. MATERIALS AND METHODS: Hospital case records of patients with histopathology proven MMPT registered in the radiation oncology department from January 1, 2008 to December 31, 2020 were retrospectively studied. Modified Warren-Gates criteria were used to define MMPT. Patients with MMPT of the head and neck (both an index and second primary as head-neck) were excluded from the study. Demographic and clinical details were recorded and analyzed. RESULTS: Forty-two eligible cases of non-head and neck MMPT were studied. The median age at diagnosis of an index case was 55 years (minimum 21, maximum 85) with a male to a female sex ratio of 5:37. Twelve patients had synchronous (28.57%) and 30 had metachronous (71.42%) MMPT. The average period between metachronous tumors was 77.77 months (minimum 12, maximum 312). The most common site of an index and second primary tumor was the breast (26; 61.90% and 23; 54.76%, respectively). Seventeen (65.38%) out of 26 index breast cancer were bilateral breast cancer and nine were others. In six cases of MMPT, there was an association between the breast and cervix. CONCLUSION: Breast cancer was the most common site for both an index and second primary malignancy followed by genital cancers. With cautious monitoring and patient education, second primary tumor could be detected earlier and managed better giving a good quality of life to patients.

SYNCHRONOUS HAIRY CELL LEUKEMIA AND HEPATOCELLULAR CARCINOMA: A CASE REPORT.

Multiple primary malignant tumors are characterized by independent occurrence and development of two or more malignant neoplasms in the same patient. We present an extremely rare case of synchronous double primary malignancies, hairy cell leukemia and hepatocellular carcinoma with lethal outcome. Diagnosis of hepatocellular carcinoma was difficult due to the presence of lymphoproliferative disease, which complicated the visualization of the process using ultrasonography. Carcinomatous emboli of hepatocellular carcinoma in small pulmonary arteries without the formation of metastatic foci have led to clinical manifestations typical of pulmonary embolism, pulmonary hypertension and severe respiratory failure. In lymphoproliferative diseases it is necessary to take into account the possibility of the development of another malignant neoplasm, which can be "buried" by tumor infiltration.

High incidence combination of multiple primary malignant tumors of the digestive system.

BACKGROUND: Clinical reports of multiple primary malignant tumors (MPMTs) in the digestive system are increasing. In China, although the survival rate of patients with MPMTs is increasing, the quality of life is very low. Many patients have reached the advanced stage when the second primary tumor is found, resulting in no early intervention and treatment. This is due to the misunderstanding of MPMTs by clinicians, who treat such tumors as metastases. Therefore, before a patient has a second primary tumor, doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient. AIM: To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization. METHODS: A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively. They were divided into metachronous MPMT and synchronous MPMT groups, and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted. Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test, respectively. A P value < 0.05 was considered as statistically significant, and SPSS version 26.0 (SPSS Inc., Chicago, Illinois, United States) was used for statistical analysis. RESULTS: Among the 1902 patients with MPMTs confirmed by pathology, 1811 (95.2%) cases were secondary primary cancers, 89 (4.7%) cases were tertiary primary cancers, and 2 (0.1%) cases were quaternary primary cancers. Most (88.2%) of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer. The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows: Breast cancer, thyroid cancer, nonuterine cancer, lung cancer, colon cancer, kidney cancer, uterine cancer, bladder cancer, rectal cancer, and gastric cancer. The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer (11.6%), the highest incidence rate of the second primary cancer was still lung cancer (24.9%), the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer (32.7%), and the highest incidence rate of the second primary cancer was lung cancer (20.8%). Among them, breast cancer, nonuterine cancer and uterine cancer were female-specific malignant tumor types, and thyroid cancer also accounted for 79.6% of female patients. The top five metachronous cancer combinations, independent of female-specific malignant tumor types and thyroid cancer, were colon cancer and lung cancer (26 cases), kidney cancer and lung cancer (25 cases), rectal cancer and lung cancer (20 cases), gastric cancer and lung cancer (17 cases), and bladder cancer and lung cancer (17 cases). The most common synchronous cancer combination was colon cancer and rectal cancer (15 cases). CONCLUSION: Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Quadruple metachronous primary cancer in a single patient: A rare case report.

Multiple primary cancer is a condition where multiple occurrences of different malignancies occur in the same individual. As there is a rise in the long-term survival of patients, multiple primary cancer is now not a rare entity. To see four different tumors in the same patient is very rare, and here, we report the case of a 60-year-old female patient with quadruple primary cancer of bilateral breast, esophagus, and sarcoma of the leg.

Landscapes of synchronous multiple primary cancers detected by next-generation sequencing.

An increase in the detection rate of multiple primary cancers has been accompanied with declining cancer death rates over the past few decades. However, synchronous multiple primary tumors have gradually increased, and the molecular mechanisms involved in the synchronous occurrence of multiple primary cancers of different origins are unclear. To investigate these mechanisms, we sequenced cancer tissues by FoundationOne CDx. Data were annotated with annovar, and we then performed pathway enrichment analysis. A total of 109 genes that were mutated in all samples were clustered into different diseases, biological processes, and molecular functions. GO and KEGG analyses indicated that the P53 and PKB signaling pathways may be relevant to the occurrence of synchronous multiple primary cancers. In summary, patients with a concordance of mutations in pathogenetic genes may have a higher risk of developing a second cancer. Our research may provide a basis for the development of individualized treatments for synchronous multiple primary cancers.

The Clinical Impact of Synchronous and Metachronous Other Primary Cancer in Gastric Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: The present study evaluated the clinical characteristics and prognostic factors of gastric cancer (GC) patients with synchronous and metachronous other primary cancer who received curative treatment for GC. PATIENTS AND METHODS: The study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A total of 244 patients were included in this study. Among them, 58 patients were diagnosed with synchronous and metachronous other primary cancer. When comparing the patient background characteristics and clinical course between GC patients without and with synchronous and metachronous other primary cancer, the background, postoperative surgical complications, and details of adjuvant treatment were similar between the two groups. The 3- and 5-year OS rates in GC patients with synchronous and metachronous other primary cancer were 69.7% and 48.0%, respectively, while those in patients without synchronous and metachronous other primary cancer were 80.6% and 74.3%, respectively, showing a statistically significant difference (p<0.001) The synchronous and metachronous other primary cancer status was included in the final multivariate analysis model (hazard ratio=2.201; 95% confidence interval=1.229-3.942; p=0.008). CONCLUSION: Synchronous and metachronous other primary cancer status is a prognostic factor in GC patients. Therefore, synchronous and metachronous other primary cancer patients need both other primary cancer and GC follow-up to improve their survival.

[Progress in clinical diagnosis and treatment of multiple primary lung cancer].

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

A Descriptive Study of the Types and Survival Patterns of Saudi Patients with Multiple Primary Solid Malignancies: A 30-Year Tertiary Care Center Experience.

BACKGROUND AND OBJECTIVE: Cancer survival has improved significantly, which reflects the achievements in screening, diagnosis, and treatment. As a consequence, multiple primary malignancies are diagnosed more frequently, with an incidence ranging from 0.52-11.7%. The types of malignancy that coexist and survival patterns vary notably in different countries and geographical areas. Due to the limited literature in Saudi Arabia, a baseline of prevalent malignancy combinations and their survival patterns would support early detection and disease management. METHOD: This was a retrospective descriptive study conducted from 1993-2022 at King Abdulaziz Medical City, Department of Medical Oncology, Riyadh, Saudi Arabia. Patients with at least two biopsy-proven solid malignancies were included. Patients with hematological malignancies, missing data, or an uncertain or indecisive pathology report were excluded. RESULT: In total, 321 patients were analyzed. More than half (57.3%) of the patients were female. A third (33%) of the cases were synchronous, and 67% were metachronous. The most frequent site of the first primary malignancy was breast cancer, followed by colorectal, skin, and thyroid cancers. The most frequent site of the second primary malignancy was colorectal cancer, followed by thyroid, breast, and liver cancers. Only 4% of the cases had a third primary malignancy, with colorectal and appendiceal cancers being the most frequent. The most frequently observed histopathology in the synchronous and metachronous malignancies was adenocarcinoma. Breast-colorectal, breast-thyroid, and kidney-colorectal were the most frequently observed malignancy combinations. CONCLUSION: The current study offers a baseline of multiple primary malignancies in Saudi Arabia and provides supporting evidence that the pattern of multiple primary malignancies varies among different countries and ethnicities. The possibility of developing another primary malignancy should be considered when treating and monitoring cancer patients.