Multiple Primary Cancers Research Articles

Treatment strategies for patients over 80 years of age with oral squamous cell carcinoma

ObjectiveTo analyze the clinical characteristics of patients with oral squamous cell carcinoma aged ≥80 years, focusing on surgical treatments. Study DesignWe reviewed patients with oral squamous cell carcinoma aged ≥80 years who underwent surgery between 2005 and 2018. Basic information, comorbidities, multiple primary cancers, initial treatment, complications, and outcomes were evaluated. ResultsOf 197 patients aged ≥80 years, 119 patients underwent surgery (50 males, 69 females; mean age: 83.5 years). The gingiva was the most common primary tumor site (63 patients, 52.9%). The stage classification was stage I in 35 patients (29.4%), stage II in 44 (37%), stage III in 16 (13.4%), stage IVA in 22 (18.5%), and stage IVB in 2 (1.7%). Comorbidities were identified in 112 patients (94.1%). Surgery was the initial treatment in 111 patients (93.3%). Eight (6.7%) patients received postoperative adjuvant chemotherapy/radiotherapy; 20 patients (16.8%) underwent free tissue transplantation. Perioperative complications were observed in 36 patients (30.3%). The cumulative 5-year and 10-year overall survival rates were 82% and 68.3%, respectively; the disease-specific survival rates were 90%. ConclusionGood treatment outcomes were obtained with radical surgery. Surgery should be the first choice if quality of life is assured and there are no issues with surgical tolerance, regardless of age.

Li-Fraumeni Syndrome: Imaging Features and Guidelines.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant familial cancer syndrome caused by germline mutations of the tumor protein p53 gene (TP53), which encodes the p53 transcription factor, also known as the "guardian of the genome." The most common types of cancer found in families with LFS include sarcomas, leukemia, breast malignancies, brain tumors, and adrenocortical cancers. Osteosarcoma and rhabdomyosarcoma are the most common sarcomas. Patients with LFS are at increased risk of developing early-onset gastric and colon cancers. They are also at increased risk for several other cancers involving the thyroid, lungs, ovaries, and skin. The lifetime risk of cancer in individuals with LFS is greater than 70% in males and greater than 90% in females. Some patients with LFS develop multiple primary cancers during their lifetime, and guidelines have been established for screening these patients. Whole-body MRI is the preferred modality for annual screening of these patients. The management guidelines for patients with LFS vary, as these individuals are more susceptible to developing radiation-induced cancers-for example, women with LFS and breast cancer are treated with total mastectomy instead of lumpectomy with radiation to the breast. The authors review the role of imaging, imaging guidelines, and imaging features of tumors in the setting of LFS. ©RSNA, 2024 Supplemental material is available for this article.

Non-small Cell Lung Cancer with Metachronous Mutations of EGFR and ALK Genes: A Case Report and Literature Review

Multiple primary lung cancer (MPLC) refers to patients with two or more primary lesions of lung cancer. It can be divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC) based on the timing of occurrence. In recent years, the detection rate of MPLC has gradually increased. However, considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis (IM), especially when the histopathological types are identical. Given the significant differences in treatment strategies and prognosis in clinical practice currently, accurate diagnosis of MPLC is crucial for personalized precision therapy. Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors. There have been reports of coexisting mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion genes in non-small cell lung cancer, but case of EGFR mutation following an ALK mutation has not been mentioned. This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery, and reviews the relevant literature. This paper aims to deepen the understanding of mMPLC and provide clinical references for the diagnosis and treatment of such patients. .

Double Heterozygosity for Germline Mutations in Chinese Breast Cancer Patients.

Double pathogenic mutations occurring in an individual are considered a rare event. The introduction of a multiple-gene panel at Hong Kong Hereditary Breast Cancer Family Registry has allowed the identification of pathogenic variants in multiple genes, providing more information on clinical management and surveillance to the proband and their family members. Breast cancer patients who are double heterozygous (DH) for different hereditary breast and ovarian cancer syndrome (HBCO)-related genes were identified from a cohort of 3649 Chinese patients. Nine patients (0.25%) were observed to have germline DH mutations in ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, and TP53. Three probands were diagnosed with unilateral breast cancer, two patients were diagnosed with bilateral breast cancer, and four patients had multiple primary cancers. The median age for breast cancer diagnosis was an early age of 36 years. Chinese DH carriers did not show worse phenotypes or have a significantly downhill clinical presentation. However, seven out of nine (77.8%) of our DH carriers harbored a BRCA1 mutation, and four of them (44.4%) developed bilateral breast cancer, suggesting Chinese DH individuals may have a higher chance of having bilateral breast cancer than other populations (p = 0.0237).

Synchronous laryngeal cancer.

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within six months after identifying the first tumor, and those cancers that develop at more than a six-month interval are termed as metachronous multiple primary cancers. Our study comprised of a patient with synchronous laryngeal cancer with double localizations. The case was solved through surgical excision of the tumors. Histopathological and immunohistochemistry examinations revealed synchronous laryngeal cancer. Laryngeal cancer should usually be managed through surgical resection, followed by oncological treatment.

The Simultaneous Bilateral Surgical Procedure for Bilateral Primary Lung Cancer.

Objective: At present, the incidence of synchronous multiple primary lung cancer (SMPLC) is increasing, and the treatment is still a challenge. This study aims to investigate the appropriate surgical procedure for treating bilateral primary lung cancer simultaneously. Methods: A retrospective analysis was conducted on clinical data from 32 patients who underwent simultaneous bilateral lung cancer surgery in our team. This data included patient characteristics, pulmonary function indicators, surgical procedures, operation duration, chest tube removal time, postoperative hospital stay, and postoperative complications. Results: Out of the 32 patients, 15 were male, and 17 were female, with an average age of 56.4 ± 8.8 years. The average maximum diameter of the main and minor tumors was 1.8 ± 1.0 cm and 1.0 ± .5 cm, respectively. All surgeries were performed thoracoscopically through intercostal approach. The procedure for the minor tumor was performed first, followed by the main tumor operation after turning over. One case was converted to thoracotomy during the main tumor operation because of bleeding. Postoperative complications occurred in one patient. No instances of respiratory insufficiency or failure were observed after the operation, and there were no perioperative deaths or readmissions within 90 days. Conclusion: Simultaneous bilateral thoracoscopic surgery is deemed a secure and feasible option for eligible patients with bilateral primary lung cancer, and it is advisable to commence the operation on the minor tumor first.

Simultaneous bilateral video-assisted thoracic surgery is safe and feasible for multiple primary lung cancers

BackgroundThe treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial.MethodsOne hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed.ResultsThe majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2).ConclusionsSimultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

Colonic interposition with vascular anastomosis for upper digestive tract reconstruction after surgery for hypopharyngeal cancer with esophageal cancer

Objective: To investigate the feasibility, safety and effectiveness of colonic interposition with vascular anastomosis in reconstructing the entire esophagus and hypopharynx after resection of hypopharyngeal cancer with esophageal cancer. Methods: We conducted a retrospective analysis of 4 male patients with simultaneous multiple primary cancers of the hypopharynx and esophagus, aged 47 to 58, treated in the Department of Head and Neck Surgery at the Hunan Cancer Hospital from February to August 2019. All cases underwent total hypopharyngectomy and total esophagectomy, of whom, three cases presented with total laryngectomy and one case with larynx preservation. Colonic interposition was performed using the left colic artery as a pedicle, with an average colonic length of 48.5 cm. The colon was elevated through the esophageal bed to the neck, and the branch of the colonic mesenteric artery was anastomosed to one of the neck arteries, including the inferior thyroid artery in one case, the transverse cervical artery in two cases, and the superior thyroid artery in one case, and all venous anastomoses were performed with the internal jugular veins. Results: The postoperative neck and abdominal wounds healed well without anastomotic leakage, and all patients were able to resume a regular oral diet within 21-30 days postoperatively. During the follow-up of 48-52 months, two cases died due to tumor recurrence, while the remaining two cases were disease-free survivals. Conclusion: Colonic interposition with vascular anastomosis is a safe and reliable reconstruction method suitable for repairing long-segment upper digestive tract defects after resection of hypopharyngeal cancer with esophageal cancer.

Single cell transcriptomic analysis reveals tumor immune infiltration by NK cells gene signature in lung adenocarcinoma

BackgroundNatural Killer (NK) cells are vital components of the innate immune system, crucial for combating infections and tumor growth, making them pivotal in cancer prognosis and immunotherapy. We sought to understand the diverse characteristics of NK cells within lung adenocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses. MethodsUsing the scRNA-seq dataset for multiple primary lung cancers (MPLCs), we examined two major NK cell groups, NK1 and NK2, comparing the expression profiles of 422 differentially expressed NK signature genes. We identified eight genes (SPON2, PLEKHG3, CAMK2N1, RAB27B, CTBP2, EFHD2, GOLM1, and PLOD1) that distinguish NK1 from NK2 cells. A prognostic signature, the NK gene signature (NKGS) score, was established through LASSO Cox regression. High NKGS scores were linked to poorer overall survival in TCGA-LUAD patients and consistently validated in other datasets (GSE31210 and GSE14814). ResultsFunctional analysis revealed an enrichment of genes related to the TGF-β signaling pathway in the high NKGS score group. Moreover, a high NKGS score correlated with an immunosuppressive tumor microenvironment (TME) driven by immune evasion mechanisms. We also observed reduced T-cell receptor (TCR) repertoire diversity in the high-risk NKGS group, indicating a negative association between inflammation and risk score. ConclusionThis study introduced the innovative NKGS score, differentiating NK1 from NK2 cells. High NKGS scores were associated with the TGF-β pathway and provided insights into LUAD prognosis and immune activities.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

A Linear Relationship between the Number of Cancers among First-Degree Relatives and the Risk of Multiple Primary Cancers.

With advances in the early detection and treatment of cancer, the incidence of multiple primary cancers (MPC) or second primary cancers has increased over time. Characterization of etiologic risk factors, including family history of cancer, within the general population is critical for assessing MPC risk in patients. We examined the association between family history of cancer among first-degree relatives and MPC risk in a prospective study of 139,958 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox proportional hazard models were used to calculate HRs and 95% confidence intervals (95% CI), adjusting for potential confounders. Over a median follow-up of 16 years (IQR: 11-19 years), 6,170 participants were diagnosed with MPC. Having a family history of cancer increased the risk of MPC by 18% (HR, 1.18; 95% CI, 1.12-1.24). A positive linear trend was observed between the reported number of cancers in the family history and MPC risk with HRs (95% CI) of 1.13 (1.07-1.20), 1.23 (1.14-1.33), 1.29 (1.15-1.45), and 1.42 (1.20-1.70) for one, two, three, and four or more cancers among first-degree relatives, respectively (Ptrend = 2.36 × 10-13). No significant differences were observed by cancer histology or specific cancer types reported in the family history. Our study demonstrates that the family history of cancer is an important risk factor for the development of MPCs and that a comprehensive assessment of the number of cancers reported among first-degree relatives may identify those at higher risk who may benefit from targeted cancer prevention and screening strategies. Prevention Relevance: Our study makes a substantial contribution to the understanding of risk factors for MPCs in the general population. It demonstrates that individuals with a strong family history of cancer are at higher risk for MPCs and may benefit from more targeted cancer prevention and screening interventions.

Incidence and Characteristics of Multiple Primary Cancers: A 20-Year Retrospective Study of a Single Cancer Center in Korea.

Rising cancer survival rates have led to an increased risk of multiple primary cancers (MPCs). Data on MPCs in South Korea are limited. This study aimed to address incidence and clinical characteristics of MPCs in a single cancer center in Korea during a 20-year period. We retrospectively analyzed 96,174 cancer patients at the Korea Cancer Center Hospital between 2003 and 2022, identifying 2167 patients with metachronous MPCs based on Surveillance, Epidemiology, and End Results SEER criteria. We categorized patients by cancer type (15 major solid cancer groups and 3 major hematologic cancer groups), including pathological diagnosis, assessed latency periods, and relative risks (RRs) for developing MPCs. The overall MPC incidence was 2.3%. Breast cancer (15.7%) was the most common primary cancer, and lung cancer (15.2%) was the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years. Decreasing latency periods for third and fourth primary cancers were observed (2.1 years and 1.6 years, respectively). Most cancers maintained their dominant pathological type despite notable changes in the prevalence of specific pathologies for certain types of second primaries. Lymphoma showed the highest RR (2.1) for developing MPCs. Significant associations were found between specific primary and subsequent cancers, including breast-ovary, thyroid-breast, stomach-pancreas, colorectal-head and neck, lung-prostate, and lymphoma-myeloid neoplasms. These findings contribute to a better understanding of MPC occurrence. They can inform future research on their etiology and development of improved management strategies.

Multivariate analysis and construction and validation of a nomogram model from data of 1610 patients with non-tumor-related anastomotic stenosis after rectal cancer surgery

Objective: To assess the risk factors affecting development of non-tumor- related anastomotic stenosis after rectal cancer and to construct a nomogram prediction model. Methods: This was a retrospective study of data of patients who had undergone excision with one-stage intestinal anastomosis for rectal cancer between January 2003 and September 2018 in Nanfang Hospital of Southern Medical University. The exclusion criteria were as follows: (1) pathological examination of the operative specimen revealed residual tumor on the incision margin of the anastomosis; (2) pathological examination of postoperative colonoscopy specimens revealed tumor recurrence at the anastomotic stenosis, or postoperative imaging evaluation and tumor marker monitoring indicated tumor recurrence; (3) follow-up time <3 months; and (4) simultaneous multiple primary cancers. Univariate analysis using the χ2 or Fisher's exact test was performed to assess the study patients' baseline characteristics and variables such as tumor-related factors and surgical approach (P<0.05). Multivariate analysis using binary logistic regression was then performed to identify independent risk factors for development of non-tumor-related anastomotic stenosis after rectal cancer. Finally, a nomogram model for predicting non-tumor-related anastomotic stenosis after rectal cancer surgery was constructed using R software. The reliability and accuracy of this prediction model was evaluated using internal validation and calculation of the area under the curve of the model's receiver characteristic curve (ROC). Results: The study cohort comprised 1,610 patients, including 1,008 men and 602 women of median age 59 (50, 67) years and median body mass index 22.4 (20.2, 24.5) kg/m². Non-tumor-related anastomotic stenosis developed in 121 (7.5%) of these patients. The incidence of non-tumor-related anastomotic stenosis in patients who had undergone neoadjuvant chemotherapy, neoadjuvant radiotherapy, and surgery alone was 11.2% (10/89), 26.4% (47/178), and 4.8% (64/1,343), respectively. Neoadjuvant treatment (neoadjuvant chemotherapy: OR=2.455, 95%CI: 1.148-5.253, P=0.021; neoadjuvant chemoradiotherapy, OR=3.882, 95%CI: 2.425-6.216, P<0.001), anastomotic leakage (OR=7.960, 95%CI: 4.550-13.926, P<0.001), open laparotomy (OR=3.412, 95%CI: 1.772-6.571, P<0.001), and tumor location (distance of tumor from the anal verge 5-10 cm: OR=2.381, 95%CI:1.227-4.691, P<0.001; distance of tumor from the anal verge <5 cm: OR=5.985,95% CI: 3.039-11.787, P<0.001) were identified as independent risk factors for non-tumor-related anastomotic stenosis. Thereafter, a nomogram prediction model incorporating the four identified risk factors for development of anastomotic stenosis after rectal cancer was developed. The area under the curve of the model ROC was 0.815 (0.773-0.857, P<0.001), and the C-index of the predictive model was 0.815, indicating that the model's calibration curve fitted well with the ideal curve. Conclusion: Non-tumor-related anastomotic stenosis after rectal cancer surgery is significantly associated with neoadjuvant treatment, anastomotic leakage, surgical procedure, and tumor location. A nomogram based on these four factors demonstrated good discrimination and calibration, and would therefore be useful for screening individuals at risk of anastomotic stenosis after rectal cancer surgery.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study

PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Treatment algorithm for metastatic malignancies in the lower extremities.

A high prevalence of proximal femoral metastases persists in patients with cancer, particularly regarding lower extremity fractures. This study offers a detailed analysis of clinical characteristics of patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies for metastatic malignancies. A total of thirty patients who underwent treatment of impending and pathological fractures at Kindai University Hospital (Osakasayama, Japan) were included. The retrospective study comprised parameters including age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome and follow-up period. Post-treatment MSTS scores were compared in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. In addition, one-year postoperative survival rates were calculated. Furthermore, operative time, blood loss and survival rates were compared between impending and pathological fractures. The participants' median age was 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck and other locations. Pathologies included multiple myeloma and unknown primary, lung, breast, kidney, liver, gastric, esophageal and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases) and compression hip screw (3 cases), among others. A negative correlation (R=-0.63) existed between MSTS and pre-fracture ECOG-PS scores. The operative time was significantly shorter in impending than in pathological fractures, with impending fractures showing significantly lower blood loss. The treatment algorithm for malignant bone tumors of the lower extremity provided in the present study was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery.

Timing of genetic testing referral and genetic testing results in patients with multiple primary cancers.

10592 Background: An individual diagnosed with a metachronous or synchronous cancer that arises independently, not due to recurrence or metastasis, has multiple primary cancers (MPC). Practice guidelines recommend germline genetic testing based on specific combinations of primary cancers and ages of diagnoses but do not recommend testing for all patients with MPC. In prior work (PubMed ID 37276540), we found that patients with breast cancer are more likely to receive testing than patients with other primary cancer types. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral. Methods: Using Oncoshare, a breast cancer research database that integrates data from electronic medical records and the California Cancer Registry, we identified female patients with MPC diagnosed between January 2000 and June 2023 with breast cancer as either the first or second cancer and seen at Stanford University. We analyzed testing rates after first vs. second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and the timing of breast cancer (1st or 2nd), using both univariate and multivariable logistic regression that adjusted for age at first diagnosis, race/ethnicity, and time between the first and second diagnoses. Results: 1,069 patients met the study eligibility; 75% were non-Hispanic White, and 73% had breast as the first cancer. 342 (32%) patients had testing, and 113 (33%) had at least one PV. Most patients had testing after the first cancer (44%, n=150) or after the second cancer (48%, n=165) (Table). Those with breast cancer as their first primary tended to have a higher testing rate, (OR 1.62, 95% CI 0.9-3.0), however, the statistical significance of this association was attenuated in the multivariable model with more parameters (P=0.11), possibly due to small sample size. Overall PV yield (33%) was high, consistent with a tertiary referral center. Conclusions: In this academic clinic-based sample of patients with MPC, we observed a higher testing rate when breast vs. another cancer was the first primary although it did not reach statistical significance. Additional research is needed to validate this finding in a larger cohort and determine whether similar referral patterns are observed in community practice, where most U.S. patients receive cancer care. [Table: see text]

Comprehensive germline and somatic DDR genomic profiles of Chinese patients with multiple primary lung cancer.

e20019 Background: The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. Disruption of the DNA damage repair (DDR) gene is related to cancer risk, progression, and treatment selection. However, the characteristics and significance of DDR alterations remain undefined in MPLC. Methods: A total of 133 Chinese MPLC patients with 308 lesions were enrolled and 784 single-focus lung cancer (SFLC) patients were analyzed as a control in the present study. Genetic testing was performed by utilizing the next-generation sequencing (NGS) of 808 cancer-related genes including 276 DDR genes. The patients were divided into 3 groups: DDR-germline (germline variants, N = 11), DDR-somatic group (somatic variants, N = 98), and the non-DDR group (no DDR variants, N = 24). Results: The overall DDR variants were identified in 82.0% (109/133) of the patients, and a total of 283 variants were found, with almost all being somatic (254/283). The most commonly germline alterations were found in RAD50 (1.5%), WRN (1.5%) and BRCA2 (0.8%), while in the somatic mutations, TP53 (26.3%) showed the highest frequency. DDR-somatic group was more likely to have alterations in TP53, LRP1B, ERBB2 and MYC compared with DDR-germline group. Taken non-DDR group as reference, mutations in TP53 (P&lt;0.05), ALK and PIK3CA were more common in DDR-germline group, but EGFR, RBM10, TP53, LRP1B, TERT and MYC (all P&lt;0.05) in DDR-somatic group. Furthermore, the DDR-somatic group exhibits the highest median tumor mutational burden (6.56) compared with 3.55 (P&lt;0.01) in DDR-germline and 3.69 (P&lt;0.01) in non-DDR group. In addition, the copy number variation (CNV) was statistically different among the three groups (P&lt;0.001). The proportion of copy number gain patients in DDR-somatic group is the highest (28.3%) compared with 12.0% in DDR-germline group and 10.9% in non-DDR group (P&lt;0.01). DDR-somatic MPLC and SFLC patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in TP53, RBM10, KRAS, BRAF, and ALK (all P&lt;0.05). Moreover, we also found notable differences in the prevalence of TP53 and CNV (both P&lt;0.05) between DDR-germline MPLC and SFLC patients. Conclusions: MPLC patients exhibit a distinctive DDR mutations landscape. The differences in the mutation profile between the DDR-germline and DDR-somatic groups and the distinct actionable genes may indicate the different target-therapy choices for MPLC patients.

Comprehensive genomic and transcriptomic profiling of pulmonary nodules in synchronous multiple primary lung cancer.

e20022 Background: Synchronous Multiple Primary Lung Cancer (sMPLC) exhibits distinct histopathological characteristics among pulmonary nodules. However, a comprehensive understanding of the somatic mutation landscape and transcriptome heterogeneity is lacking. Therefore, our study aims to meticulously investigate genomic distinctions among multiple pulmonary nodules within individual patients. Methods: We performed targeted sequencing on tumor specimens and conducted bulk RNA transcriptome analysis on 53 multiple nodules originating from 26 lung cancer patients. The multiple nodules from the same patient was determined as major nodule and minor nodule. Additionally, the tumor tissues underwent histopathological evaluation through H&amp;E staining, complemented by a comprehensive series of immunohistochemistry (IHC) analyses to detect protein expression. The detected protein markers encompassed PD-L1, Ki67, and others. Results: For the 53 nodule samples from 26 MPLCs patients, EGFR was the mostly mutated genes, and the TP53 mutation frequency demonstrated notably different between major and minor nodules. Furthermore, pathway enrichment analysis based on the differentially expressed genes (DEGs) between major and minor nodules revealed the significantly active cell cycle and p53 pathways in the major nodules. Additionally, both major and minor nodules demonstrated mostly similar immune microenvironment and PD-L1 protein expression, and a significantly higher expression of Ki67. A noteworthy suppression was observed in the immune microenvironment in nodules, revealed by the expression of macrophage, neutrophils, and NK cells. Furthermore, minor nodules exhibited a modestly elevated expression of macrophages compared to major nodules. Additionally, among the significantly up-regulated cell cycle related genes in the major nodules when compared with minor nodules, CCNE1 mRNA expression demonstrated significant correlation with poor prognosis in the lung cancer. Conclusions: This study validated molecular distinctions between samples from major and minor nodules in patients with sMPLC at both genomic and transcriptomic levels. The major nodules exhibited heightened activity in tumor cell proliferation pathways and demonstrated malignancy-related biological characteristics, which correlated with pathological assessment results.

Similarities and differences of lung cancer (LC) multidisciplinary teams (MDTs) in China compared to Europe and Canada.

e13562 Background: LC MDTs involve a collaborative approach where specialists work together to analyze individual cases, discuss treatment options, and tailor comprehensive care plans for patients. Implementing MDTs can be challenging, especially for developing countries with limited resources and high disease burden. China, with approximately 820,000 new patients with lung cancer in 2020 accounting for 37% of the total number in the world, bears the responsibility of treating the largest lung cancer patient population worldwide. The global MDT Aid Program (MAP) in LC has been including China to gather insights on the challenges, best practices, similarities, and differences of China LC MDT processes compared to other countries, so as to improve the outcome and cost-efficiency of global MDTs. Methods: In this study, we learned about the status, best practices, challenges of LC MDT development in China through virtual semi-structured healthcare professional (HCP) interviews, on-site masterclasses, and internal data sharing with 3 Chinese leading hospitals in LC - Guangdong Provincial People’s Hospital, West China Hospital and Xiangya Hospital. Similarities and differences were gathered based on previous MAP experience and insights from HCP discussions in LC across the Netherlands, Italy, Spain, Switzerland, Denmark, Norway, and Canada. To build a global collaboration on LC MDTs, three international knowledge exchange (IKE) sessions were organised to include China and all participating countries. Results: We identified seven main differences between China, Europe and Canada, including the enrolment criteria of patients in MDT that China MDTs focus on challenging cases such as resistance to multi-lines of therapy, multiple primary lung cancer and stage III lung cancer, while Europe and Canada MDTs mainly for routine patients. Other differences include setup and composition of MDT teams, digitalization of MDTs, incentives and reimbursement for MDT attendance, cross-institutional patient referral to the MDT, time spent per patient, patient follow-up after MDT discussion. Similarities identified include the MDT development model from both hospital and national level, experience sharing to educate junior physicians, hospital willingness to learn at global level, and challenges of high pressure with limited medical resources. Best practices of leveraging innovative digital capabilities to improve MDT efficiency and to support decision-making have been shared by China participants during the IKEs. Conclusions: Global collaboration to identify synergies within LC MDT communities can help China and other regions learn from each other and share China expertise in large-volume data-based practices globally. Alongside China’s rapid development of digital health, the digitalization of MDTs is likely to follow.

Adherence to cancer screening for patients with Li-Fraumeni syndrome: A report on our experience at Fred Hutchinson Cancer Center.

e22553 Background: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome where patients are at risk of developing multiple primary cancers, synchronous, and metachronous cancers in their lifetimes. Patients with LFS often serve as their own advocates to request and receive appropriate cancer screening as few clinicians have experience in caring for them and few clinics are adequately staffed to provide complex cancer screening coordination. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. In July 2020, Fred Hutch's clinical cancer genetic service launched a high-risk surveillance clinic for patients with hereditary cancer syndromes requiring services from multiple specialties. Our clinic has since helped patients with LFS receive coordinated cancer screening. Here we report on adherence to the Toronto protocol by reviewing patient demographic, cancer history and family history, and genetic records. Furthermore, we report on the number of visits, types of screening, and cancer diagnoses patients with LFS received since enrolling in the high-risk clinic. Results: A total of 112 patients with LFS were seen in the high-risk surveillance clinic between July 2020 and December 2023. Of these patients’ paths reviewed so far, 73 patients established with the clinic and received blood work and/or MRI imaging scans, and 42 were seen in at least one follow up visit. 2 patients with LFS were diagnosed with one or more new cancer diagnosis since enrollment, both have completed treatment, and both are without evidence of disease as of February 2024. Conclusions: The high-risk surveillance clinic was promptly utilized by patients with LFS for coordination of their complex cancer screening needs and to guide their next steps when triaging symptoms and concerns. While the clinic addresses a gap in cancer screening coordination, patients with LFS need wrap around care close to where they live which is difficult to accomplish in the Pacific Northwest.