PMID: 35356148 PMCID: PMC8959409 DOI: 10.3389/fendo.2021.752176

Abstract

Background:

The overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low,
and it is pretty hard to treat bone metastasis. However, there are currently no effective nomograms to predict the diagnosis and prognosis
of pancreatic cancer with bone metastasis (PCBM). Therefore, it is of great significance to establish effective predictive models to guide clinical practice.

Methods:

We screened patients from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2016.
The independent risk factors of PCBM were identified from univariable and multivariable logistic regression analyses, and univariate and
multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors affecting the prognosis of PCBM.
In addition, two nomograms were constructed to predict the risk and prognosis of PCBM. We used the area under the curve (AUC), C-index,
and calibration curve to determine the predictive accuracy and discriminability of nomograms. The decision curve analysis (DCA) and Kaplan-Meier
(K-M) survival curves were employed to further confirm the clinical effectiveness of the nomogram.

Results:

Multivariable logistic regression analyses revealed that risk factors of PCBM included age, primary site, histological subtype,
N stage, radiotherapy, surgery, brain metastasis, lung metastasis, and liver metastasis. Using Cox regression analyses, we found that independent prognostic
factors of PCBM were age, race, grade, histological subtype, surgery, chemotherapy, and lung metastasis. We utilized nomograms to visually express data analysis
results. The C-index of training cohort was 0.795 (95%CI: 0.758-0.832), whereas that of internal validation cohort was 0.800 (95%CI: 0.739-0.862), and the external
validation cohort was 0.787 (95%CI: 0.746-0.828). Based on AUC of receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis
(DCA), we concluded that the risk and prognosis model of PCBM exhibits excellent performance.

Conclusion:

Nomogram is sufficiently accurate to predict the risk and prognostic factors of PCBM, allowing for individualized clinical decisions
for future clinical work.

Keywords:

Cox regression; Surveillance Epidemiology and End Results (SEER) database; bone metastasis; logistic regression; nomogram; pancreatic cancer; predictors.

Detection Methods for Metastatic Pancreatic Cancer

Detecting metastatic pancreatic most cancers entails a mixture of imaging, blood exams, and tissue sampling. These techniques assist discover the unfold of most cancers past the pancreas to organs just like the liver, lungs, or bones. Early detection of metastasis is essential for making plans powerful treatment.

Imaging Techniques

Imaging is a key device in detecting the unfold of pancreatic most cancers.

• CT Scan (Computed Tomography):Provides special cross-sectional photos of the pancreas and surrounding organs.Useful for recognizing metastasis withinside the liver, lungs, or lymph nodes.
• MRI (Magnetic Resonance Imaging):Offers excessive-assessment photos to locate smaller lesions and metastases, in particular in gentle tissues.
•  PET Scan (Positron Emission Tomography):Detects cancerous interest the use of radioactive tracers.Often mixed with a CT scan (PET-CT) for specific place of metastases.

Ultrasound:

• Endoscopic Ultrasound (EUS): A minimally invasive technique to evaluate neighborhood unfold and lymph node involvement.
• Abdominal Ultrasound: Helps locate liver metastases or ascites (fluid buildup).
• Bone Scan:Used while bone metastasis is suspected, figuring out regions of excessive bone interest related to most cancers unfold.

Blood-Based Biomarkers

Blood exams can imply the presence or development of metastatic pancreatic most cancers.

• CA 19-9 (Carbohydrate Antigen 19-9):A generally used tumor marker for pancreatic most cancers. Elevated stages might also additionally imply sickness development or metastasis.
• CEA (Carcinoembryonic Antigen):Another marker that can upward push with metastasis, aleven though much less precise than CA 19-9.
• Complete Blood Count (CBC):Detects anemia or expanded white blood mobileular count, which might also additionally imply systemic most cancers effects.
• Liver Function Tests (LFTs):Assess liver involvement while metastasis to the liver is suspected.

Biopsy and Tissue Analysis

Tissue sampling is accomplished to verify metastasis.

• Fine-Needle Aspiration (FNA):Often guided with the aid of using EUS or CT to pattern suspected metastatic sites.
• Core Needle Biopsy:Collects large tissue samples for greater special evaluation of metastatic lesions.
• Liquid Biopsy:Examines circulating tumor DNA (ctDNA) or most cancers cells withinside the bloodstream, presenting a non-invasive manner to evaluate metastasis.

 Advanced Molecular and Genetic Testing

• Next-Generation Sequencing (NGS):Detects genetic mutations or markers in most cancers cells, supporting discover metastasis and manual centered therapy.
• Immunohistochemistry (IHC):Used on biopsy samples to locate proteins related to metastasis and tumor type.

Stages of Metastatic Pancreatic Cancer

Metastatic pancreatic most cancers takes place while the most cancers has unfold from the pancreas to remote elements of the body, including the liver, lungs, or bones. This is assessed as Stage IV pancreatic most cancers, which represents the maximum superior degree of the sickness. Below is an outline of the way staging works and what it approach for metastatic pancreatic most cancers.

How Pancreatic Cancer Is Staged

Doctors stage pancreatic cancer to determine how far the disease has spread, helping them decide the best treatment approach. They most commonly use the TNM system to measure pancreatic cancer:

• T (Tumor): This a part of the staging device makes a speciality of the scale and volume of the number one tumor. It describes whether or not the most cancers has invaded close by tissues or organs.
• N (Nodes): This shows whether or not the most cancers has unfold to nearby lymph nodes. which can be small glands that assist combat infection. Lymph node involvement enables investigate how competitive the most cancers is and its capacity to unfold.
• M (Metastasis): This class is important in figuring out whether or not the most cancers has unfold to remote organs. When pancreatic most cancers has unfold past the pancreas. it’s far categorised as M1, which means the most cancers is metastatic.
  For metastatic pancreatic most cancers, the M class is constantly M1. indicating that the most cancers has unfold to remote webweb sites, regularly making remedy greater complex.

Key Characteristics of Metastatic Pancreatic Cancer (Stage IV)

Stage IV pancreatic most cancers is taken into consideration superior, and the traits of this degree offer perception into the most cancers`s conduct and progression:

• Primary Tumor (T): At this degree, the tumor can nonetheless be localized withinside the pancreas however may also have grown into close by organs or blood vessels. In a few cases, it can have unfold to the duodenum (the primary a part of the small intestine) or stomach.
• Lymph Nodes (N): Pancreatic most cancers regularly spreads to close by lymph nodes, however this isn’t always constantly the case in metastatic sickness. Even if lymph nodes aren’t involved, remote metastasis (M1) nonetheless qualifies the most cancers as Stage IV.

Distant Spread (M1):

The maximum not unusualplace webweb sites of metastasis for pancreatic most cancers are:

• Liver: The pancreas’ blood supply makes the liver the most commonly affected organ, allowing cancer cells to travel there.
• Lungs: The lungs are every other not unusualplace web website online of metastasis, and while the most cancers reaches this area, it could critically effect breathing.
• Peritoneum:The cancer can affect the lining of the abdominal cavity, often leading to ascites (fluid buildup in the abdomen), which can cause bloating, discomfort, and difficulty breathing.
• Bones: Though much less not unusualplace, metastatic pancreatic most cancers also can unfold to bones, inflicting ache and different headaches like fractures.

Treatment of Metastatic or Recurrent Pancreatic Cancer

Metastatic or recurrent pancreatic most cancers is a difficult condition, because the most cancers has unfold past the pancreas to different components of the body. At this superior stage, the number one awareness of remedy is to govern the most cancers, control signs, and enhance best of life. While a remedy isn’t always usually possible, numerous remedy alternatives can assist amplify survival and simplicity discomfort.

 Chemotherapy

Doctors most commonly use chemotherapy to treat metastatic or recurrent pancreatic cancer. It entails the usage of effective tablets to kill most cancers cells or prevent their growth. Chemotherapy is usually encouraged for sufferers who’re in desirable sufficient fitness to tolerate the facet effects.

Common chemotherapy regimens include:

• FOLFIRINOX: A aggregate of 4 chemotherapy tablets (fluorouracil, leucovorin, irinotecan, and oxaliplatin). Doctors regularly use it for patients with a good performance status, and it has shown improved survival in some cases.
• Gemcitabine (Gemzar): A chemotherapy drug usually used for pancreatic most cancers. It can be used by myself or mixed with different treatments.
• Nab-paclitaxel (Abraxane): Often mixed with gemcitabine, this drug has been proven to enhance survival rates.
• Chemotherapy can assist reduce tumors, alleviate signs, and every now and then make surgical procedure or radiation possible.

Targeted Therapy

Targeted remedy pursuits to intrude with precise molecules that assist most cancers cells develop and unfold. It may be used by myself or in aggregate with chemotherapy.

• Erlotinib (Tarceva): A centered remedy drug that blocks alerts wished for most cancers cells to develop. It can be utilized in aggregate with chemotherapy for a few sufferers.
• PARP inhibitors: For sufferers with BRCA mutations, tablets like Olaparib might also additionally assist restore DNA harm in most cancers cells, slowing most cancers growth.
• Targeted remedy is regularly taken into consideration for sufferers with sure genetic mutations that make their most cancers greater attentive to precise treatments.

Immunotherapy

Immunotherapy enables the body`s immune machine understand and spoil most cancers cells. While its effectiveness in pancreatic most cancers has been limited, it is able to nonetheless play a role, mainly in sufferers with precise genetic traits including microsatellite instability-high (MSI-H) tumors.

• Checkpoint inhibitors: Drugs including Pembrolizumab (Keytruda), which assist the immune machine assault most cancers cells through blocking off the proteins that save you immune cells from spotting most cancers.
• Immunotherapy remains being studied for pancreatic most cancers, and ongoing studies maintains to discover its capability benefits.

Surgery

Surgical treatment for metastatic or recurrent pancreatic cancer is rare because cancer usually spreads too far for surgery to be effective. However, in some cases where the cancer has spread to nearby areas but remains relatively contained, doctors may consider surgery to remove the primary tumor or alleviate symptoms, such as blockages in the bile duct.

• Palliative Surgery: Aimed at improving quality of life, doctors may perform procedures like bypass surgery or stent placement to alleviate symptoms such as bile duct obstruction or gastrointestinal blockage.

Radiation Therapy

Radiation remedy makes use of high-electricity rays to goal and reduce most cancers cells. While it isn’t always a therapy for metastatic pancreatic most cancers. it could be used to alleviate signs inclusive of ache or obstruction.

• External Beam Radiation:This approachgives you radiation from out of doors the frameand mightassistreduce tumors which areinflictingache or different problems.
• Stereotactic Body Radiotherapy (SBRT) it delivers highly focused radiation to cancerous areas and is often used for localized tumors that doctors cannot remove surgically.
• Doctors typically use radiation as part of palliative care to manage symptoms or as an addition to other treatments.

Palliative Care

Palliative care performs an crucial position in handling metastatic or recurrent pancreatic most cancers. The purpose is to relieve signs and enhance the patient`s first-class of life.

• Pain Management: Pancreatic most cancers can purpose extreme ache, specially if it spreads to close by organs just like the liver or bones. Pain alleviation can also additionally contain medicinal drugs inclusive of opioids, nerve blocks, or complementary remedies like acupuncture.
• Nutritional Support: Weight loss and terrible urge for food are not unusualplace in superior pancreatic most cancers. Patients can also additionally obtain feeding tubes or oral dietary dietary supplements to hold strength.
• Ascites Management:Doctors can control fluid buildup in the abdomen (ascites) with drainage or medications like diuretics to reduce discomfort.

Clinical Trials

• Clinical trials are an critical choice for sufferers with metastatic or recurrent pancreatic most cancers. They provide get entry to to current remedies that aren’t but extensively available.
• Trials can also additionally contain new chemotherapy regimens, immunotherapies, centered remedies, or mixtures of present remedies.

Supportive Therapies

• Other supportive remedies, inclusive of psychosocial help and counseling, can assist sufferers deal with the emotional and mental strain of residing with superior most cancers. Additionally. physiotherapy can be useful for enhancing mobility and lowering fatigue..

Prognosis for Stage IV Pancreatic Cancer

Stage IV pancreatic cancer characterizes the spread of cancer to distant organs, making it the most advanced and aggressive stage of the disease. At this point, the most cancers has generally moved past the pancreas to regions just like the liver, lungs, peritoneum, or bones. Because of the significant unfold. remedy at this level is typically palliative and aimed toward enhancing fine of lifestyles, instead of curing the disease.

While the diagnosis for Stage IV pancreatic most cancers is normally poor, it’s miles vital to be aware that each affected person`s case is unique, and elements inclusive of average fitness, remedy options, and genetic profile can have an impact on outcomes.

Key Factors Affecting Prognosis

Several elements play a position in figuring out the diagnosis for sufferers with Stage IV pancreatic most cancers:

Extent of Metastasis:

• The in addition the most cancers has unfold, the greater tough it’s miles to treat. Metastasis to critical organs inclusive of the liver or lungs extensively reduces survival prospects.
  Metastasis to the peritoneum (lining of the belly cavity) is likewise not unusualplace in Stage IV and might complicate symptom management.

Response to Treatment:

• How properly a affected person responds to chemotherapy, focused cures, or different remedies can have an impact on survival rates. Some sufferers might also additionally enjoy stabilization or maybe a moderate discount in tumor size, imparting a few extension of lifestyles.

Genetic Mutations and Tumor Profile:

• BRCA mutations, KRAS mutations, and different genetic elements can have an impact on remedy response. For instance, sufferers with sure mutations might also additionally reply higher to focused cures or immunotherapy, enhancing survival outcomes.
• Microsatellite instability-high (MSI-H) tumors are much more likely to reply to immunotherapy, imparting capacity blessings for a few sufferers.

Overall Health and Performance Status:

• The affected person`s wellknown fitness, age, and overall performance status (how properly they are able to carry out every day activities) have an effect on diagnosis. Patients who’re in higher average fitness might also additionally tolerate competitive remedies higher, main to longer survival.

Treatment and Survival Outlook

Palliative Care

• Purpose: To enhance fine of lifestyles with the aid of using addressing signs inclusive of pain, jaundice, and digestive issues.
• Key interventions: Pain management, bile duct stenting for jaundice. ascites (fluid buildup) management, and dietary support.
• Impact: Although it doesn`t goal the most cancers itself.Palliative care is crucial for keeping consolation and dealing with debilitating signs.

Chemotherapy

• Purpose: To sluggish tumor boom and relieve signs with the aid of using shrinking tumors.
• Common Regimens: Doctors commonly use drugs such as Gemcitabine, FOLFIRINOX (a combination of drugs), and Nab-paclitaxel.
• Impact: While chemotherapy can`t therapy Stage IV pancreatic most cancers, it can expand lifestyles with the aid of using some months to a yr in a few sufferers. relying on how properly the most cancers responds.

 Targeted Therapy

• Purpose: To block unique genetic pathways that permit most cancers cells to develop and divide.
• Common Regimens:At Stage IV, while the cancer is not generally curable, various treatments can manage symptoms, slow progression, and, in some cases, extend life.
• Impact: Targeted treatments can provide big gain for sufferers .whose tumors have unique mutations. together with BRCA mutations. They may also assist enhance consequences in a few individuals, aleven though they’re now no longer a cure.

 Immunotherapy

• Purpose: To improve the body`s immune gadget to higher apprehend and assault most cancers cells.
• Medications: Checkpoint inhibitors like Pembrolizumab (Keytruda) may also assist a few sufferers. Especially people with MSI-H tumors or positive genetic mutations.
• Impact: Researchers are still studying immunotherapy for pancreatic cancer. However, some patients have shown positive responses, leading to extended survival and better quality of life..

Clinical Trials

• Purpose: To discover new and experimental remedies. together with novel chemotherapy drugs. centered treatments, or immunotherapies.
• Impact: Clinical trials provide get admission to to current remedies that won’t be broadly available. Imparting desire for sufferers who’ve exhausted wellknown options.

Survival Rates

The survival fee for Stage IV pancreatic most cancers is normally low.with maximum sufferers residing only some months after diagnosis. The median survival for Stage IV pancreatic most cancers usually stages from three to six months. aleven though a few sufferers may also stay longer with competitive remedy or participation in medical trials.
1-yr survival fee: Around 20% of sufferers continue to exist for twelve months after diagnosis.It relying on different factors together with remedy reaction and universal health.
5-yr survival fee: The universal 5-yr survival fee for Stage IV pancreatic most cancers is beneathneath 5%. This displays the competitive nature of the most cancers and its resistance to many sorts of remedy.

Research and Advances

Although the diagnosis for Stage IV pancreatic cancer remains poor, researchers are making significant strides in studies. Advances in genomic profiling, immunotherapy, and centered treatments are imparting new desire for sufferers. Clinical trials hold to analyze promising remedies, and a few sufferers are taking advantage of those current treatments.
Ongoing efforts in early detection and personalised remedy can also result in higher consequences .Withinside the future, with remedies tailor-made to the unique genetic make-up of a patient`s tumor. The goal is that as research continues, survival rates will improve, and researchers will develop more effective treatments for this challenging disease.

Conclusion:

Metastatic pancreatic most cancers gives big demanding situations. Because of its superior degree and the substantial unfold of the disorder to remote organs. While the analysis for metastatic pancreatic most cancers is normally poor, remedy options, along with chemotherapy.Focused therapies, immunotherapy, and palliative care, can assist manipulate signs and symptoms and enlarge existence for a few patients. Advances in genetic studies, personalised treatments. And medical trials provide new opportunities for enhancing outcomes.Despite the fact that a remedy stays elusive. Despite the low survival rates, ongoing traits. In most cancers studies maintain to offer wish for higher control.And capacity breakthroughs in remedy.