Lymphomas

This procedure consists of partial or total removal of one or more suspicious lymph nodes.

If the suspected lymph node is superficial and palpable, the procedure is performed in outpatient clinic with a small incision made under local anesthesia.

If, on the other hand, the lymph node is deep within the chest or abdomen, tissue harvesting can be done in two ways:

• through harvesting with minimally invasive techniques, using specific needles under the guidance of CT or ultrasound; with this method, which requires local anesthesia, it is also possible to take small fragments of tissue or of the organ in which the CT scan showed the presence of a possible lymphoma. It is important to provide the pathologist with an adequate tissue sample;
• surgery: a procedure is performed under general anesthesia to take a lymph node or tissue sample suspected for lymphoma. Again, the procedure is guided by CT or ultrasound images to be as accurate as possible.

Lymph nodes or tissue samples taken by biopsy are sent to the pathology laboratory where they undergo histologic examination which is supplemented by immunohistochemical, cytogenetic, and molecular investigations.

The diagnosis of lymphoma is complex and requires a team of pathologists, cytogeneticists, and other specialized personnel to be able to make the diagnosis of certainty and identify exactly the type and subtype of lymphoma. This is especially important because treatment depends first and foremost on the correct diagnosis, and different types of lymphoma require different therapies. It follows that such diagnoses must be placed in highly specialized centers. The Candiolo Institute is one such center that has all the latest diagnostic techniques and a team specializing in the diagnosis of lymphomas, ensuring that patients receive an accurate framing and a personalized course of treatment.

In addition to classic microscopic examination, samples taken by biopsy are subjected to molecular analysis to identify any abnormalities in tumor DNA, which allows for extremely precise characterization of the type of lymphoma.

Once the diagnosis is established, the patient must undergo some necessary tests to ascertain his or her general health status and define the extent and stage of the disease.

Blood tests are used to check the blood count and thus the possible presence of anemia, white blood cell and platelet counts, kidney and liver function, and to measure the level of certain molecules-lacticodehydrogenase (LDH) and beta-2-microglobulin-that may give information about the characteristics of the disease, for example, its aggressiveness.

These tests aim to check whether there are lymphoma cells in the bone marrow. During the procedure, which is performed under local anesthesia, the doctor inserts a needle into the top of the buttock with which he penetrates the pelvic bone and takes two small samples, one of bone marrow blood and one of bone tissue. In some types of lymphoma such as Hodgkin’s lymphoma and diffuse large cell lymphoma, this examination is no longer considered necessary, while it remains important in other types.

The collected specimens are then sent to anatomic pathology for histological examination and appropriate analysis.

CT (computerized axial tomography) is a radiological examination in which data from passing X-rays through the areas of the body to be investigated are reprocessed by a computer that returns three-dimensional images of different tissue types.

Total body CT scan (neck, chest, abdomen and pelvis) allows visualization of any deep lymph nodes affected by the disease and to calculate their size, and also allows to check for the presence of the tumor in organs such as lungs or liver.

The examination requires a contrast agent that is injected into the vein. It is performed on an empty stomach at the Division of Radiodiagnostics.

PET (positron emission tomography) is a diagnostic method in Nuclear Medicine that indicates tumor presence and activity by highlighting abnormal cell metabolism. Through the injection of a of a radioactive isotope of glucose, PET scanning can identify cancer cells because they consume more of it than healthy cells.

By measuring the rate at which cells consume glucose, with PET scanning it is therefore possible to identify all the initial sites of the disease and is a more sensitive test than CT scanning by being able to detect even very small lesions or in sites that are difficult to assess by CT, such as bone.

In addition, PET scanning is a critical for assessing response to therapy. The disappearance of areas with signs of active disease indicates a complete response to treatment in many types of lymphoma.

Lymphoma therapy may involve the use of drugs that can adversely affect the heart. Therefore, careful assessment of cardiac function through A cardiologic examination and an echocardiogram which provide indications of the presence or absence of cardiac issues to be taken into account when planning therapy for lymphoma.

For Hodgkin’s lymphoma, the Ann Arbor system of 4 stages is used:

• • Stage I: circumscribed lymphoma in a single group of lymph nodes;

• • Stage II: Lymphoma present in two or more groups of lymph nodes, all located above or below the diaphragm (the muscle that separates the chest from the abdomen);

• • Stage III: lymphoma present both above and below the diaphragm;

• • Stage IV: Lymphoma spread to other organs, such as bone marrow or liver.

At each stage, the letter A is added if there are no symptoms (night sweats, fever, weight loss), the letter B if one or more of these symptoms are present .

For non-Hodgkin’s lymphomas, in addition to the Ann Arbor stage classification, a number of internationally recognized prognostic factors, specific to the type of lymphoma, are considered to help predict the likelihood of response to treatment and survival.

These factors are compiled into true risk scores and take several elements into account:

• The extent of the disease (stage, number of lymph nodes or organs involved);

• some laboratory data, such as the presence of anemia or increased LDH protein in the blood;

• The patient’s characteristics, particularly age and general health condition (performance status).

Thanks to these parameters, it is possible to distinguish the most aggressive cases from those with more favorable course, so as to better tailor the treatment course.

The term chemotherapy refers to the drugs that eliminate cancer cells Taking advantage of their faster reproduction rate than healthy ones. Because it interferes with the replication mechanisms of cells, chemotherapy also damages the body’s healthy cells, causing side effects that fortunately often disappear once the treatment is over and are in any case well controlled with appropriate supportive therapies.

In most cases, chemotherapy is administered by intravenous injection, less frequently orally. The duration of each administration, which is performed on an outpatient or inpatient basis depending on the scheme used, can vary from minutes to hours depending on the treatment scheme involving a combination of various drugs. In various situations, it may be necessary to insert a central vascular access prior to the initiation of therapy, that is, a device that allows drugs to be delivered into a larger vein, making treatment safer.

Chemotherapy is received “in cycles”: each cycle can be administered over one or more days and is followed by a few weeks of rest. The number of cycles depends on the type of lymphoma and, of course, the response to medication, which can vary greatly from patient to patient.

Immunotherapy involves the use of drugs that can fight the disease using mechanisms similar to those of the immune system, or by restoring the ability of the patient’s own immune system to attack and destroy cancer cells.

Four main types of immunotherapy are used in lymphomas:

• Monoclonal antibodies;
• immunoconjugated antibodies;
• bispecific antibodies
• CAR T cells

Monoclonal antibodies

Monoclonal antibodies are drugs that function similarly to our body’s natural antibodies. They bind to specific proteins (receptors) on the surface of cancer cells and, in doing so, activate the immune system to destroy them, just as happens when natural antibodies fight viruses or bacteria.

An example of drugs available today are Rituximab and Obinutuzumab, which bind to the CD20 protein found in B-cell lymphomas;

These drugs are usually combined with chemotherapy to make it more effective and are administered intravenously.

Immunoconjugated drugs

Immunoconjugated drugs are monoclonal antibodies to which substances toxic to the cancer cell have been combined in the laboratory. Once administered, the antibodies recognize the markers on the cancer cells, bind to them and “dump” the toxic substance into the cancer cell, causing its death.

Examples include Brentuximab-Vedotin, which acts against the CD30 protein found in Hodgkin’s lymphoma and some T-cell lymphomas; Polatuzumab-Vedotin, directed against the CD79b protein, used in diffuse large B-cell lymphomas; and Loncastuximab-tesirine, directed against the CD19 protein.

Bispecific antibodies

Bispecific antibodies are antibodies created to recognize two proteins simultaneously, one present on cancer cells and one present on healthy cells in the patient’s immune system. The diseased cell and the healthy cell are then “approached,” and the healthy cell is induced by the drug to attack and destroy the diseased cell.

Currently available bispecific antibodies recognize the CD20 protein present on tumor cells and the CD3 protein present on healthy T lymphocytes. Examples include epcoritamab, glofitamab, and mosunetuzumab. Administration is relatively simple, often intravenously or subcutaneously. Like all drugs, bispecific antibodies can cause side effects, especially at the beginning of treatment. The most common are fever, chills, fatigue, and muscle aches. In some cases a reaction called cytokine release syndrome may appear, with flu-like symptoms, but usually manageable with appropriate treatment.

CAR-T cells

CAR-T cells are an innovative form of cell therapy. These are the patient’s own T lymphocytes (a type of white blood cell) that are taken from the blood, modified in the laboratory through genetic engineering, and reinserted into the patient with the ability to recognize and specifically destroy cancer cells.

The modification involves adding a protein called CAR (Chimeric Antigen Receptor) to T lymphocytes, which enables them to recognize the CD19 protein, found on many lymphoma cells.

This therapy is intended for younger patients, but it can also be applied to older patients up to 75-80 years of age (depending on the type of lymphoma) if they are in good general health and without other serious diseases, because it can give even major side effects.

This type of therapy is performed through a single infusion through an IV in a similar manner to a transfusion, after a short preparatory chemotherapy, and is performed in an inpatient setting to monitor side effects caused by inflammation due to the administration of the therapy. During admission, medical staff closely monitor the patient’s temperature, blood pressure, and neurological status to intervene promptly in case of reactions such as fever, chills, fatigue, or confusion. These side effects are common especially in the first few weeks after infusion and, if recognized and treated promptly, can be managed effectively.

Regular follow-ups are scheduled after discharge to assess the response to treatment and make sure the patient is recovering well.

It is important for patients and their family members to be informed about possible symptoms to report to the physician immediately to ensure safe management of therapy.

CAR-Ts are used in cases where the disease does not respond to standard treatment or returns after at least one or two conventional treatments, particularly for:

• diffuse large B-cell non-Hodgkin’s lymphoma
• mantle cell lymphoma
• follicular lymphoma

These are drugs capable of block certain specific molecular alterations that underlie the growth of certain types of lymphoma (mantle cell, lymphocytic, marginal, etc.).

These drugs are administered orally usually on a continuous basis.

Examples include Ibrutinib, Acalabrutinib, Zanabrutinib, lenalidomide, etc.

Radiation therapy is a treatment modality that uses high-energy radiation to eliminate cancer cells. In the treatment of lymphomas, it can be used as a treatment exclusive or in combination with chemotherapy and immunotherapy. It is mainly used when the lymphoma is in the early stage and is generally performed on the lymph node stations affected by the disease.

Radiation therapy is administered through a device called a linear accelerator (LINAC)., in daily sessions from Monday to Friday for several weeks. Sessions usually last about 10 to 15 minutes.

Radiotherapy treatment consists of theapplication of irradiation fields which are shaped to fit the shape of the volume to be treated and protect the surrounding healthy organs. In this way, a higher dose of radiation can be delivered to the tumor, reducing the doses to surrounding tissues.

The Intensity-modulated radiation therapy (IMRT), allows the intensity of each individual radiation beam to be modulated, ensuring a high conformation of the dose to be delivered to diseased tissues while reducing the dose delivered to healthy tissues.

In addition, thanks to the Image-Guided Radiotherapy (IGRT) it is possible to obtain in real time a precise localization of the “target” and its relationship to surrounding organs and thus ensure that the patient is in the same position during each treatment fraction.

Stem cell transplantation is a treatment reserved for some cases in which lymphoma does not respond to standard treatment or reappears after therapy. The use of transplantation is now less common with the introduction of more effective immunotherapies such as CAR-T or bispecific antibodies.
Its goal is to enable the use of high-dose chemotherapy, stronger than normally tolerated, so as to achieve maximum effectiveness against the tumor.

Because these high doses severely damage the bone marrow (the organ that produces blood cells and stem cells), transplantation is performed, which allows the marrow to regenerate.

Types of transplantation

• Autologous transplantation (most common in lymphomas): stem cells are harvested from the patient himself and then reinfused;

• Allogeneic transplantation: stem cells come from a matched donor.

How autologous transplantation takes place

1. Stem cell stimulation: a protein called growth factor, which increases stem cell production, is given to the patient via subcutaneous injections;

2. collection (staminopheresis): stem cells are taken from the blood through a procedure similar to a blood donation and then frozen;

3. High-dose chemotherapy: the patient receives intensive therapy to eliminate cancer cells;

4. Reinfusion: previously collected stem cells are reinfused into the patient’s blood to repopulate the bone marrow.

After transplantation

For about 12 to 15 days, white blood cells remain very low until the marrow resumes production. During this period, the patient is admitted to a protected room at the transplant center to minimize the risk of infection.

All cancer treatments involve side effects that impact the patient’s quality of life more or less severely.

Treatments for lymphomas also involve major side effects, both physical and psychological, that change the way people cope with daily life.

At the Candiolo Institute, attention to the patient’s quality of life remains a priority throughout the entire course of treatment: the physicians and nurses of the multidisciplinary team are available to provide the patient with all the support needed to manage the various side effects, particularly through nutritional counseling, psychological support, and pain therapy.

To ensure timely and direct support and receive timely answers to concerns and questions, a dedicated helpline is in place at the Candiolo Institute for all patients.

From Monday to Friday, from 8 a.m. to 5 p.m., you can contact the secretariat of the oncology day hospital at 011.993.3775, reporting the need for urgent consultation.

The patient will be quickly put in touch with his or her medical specialist, to receive clear answers and immediate support.

The cancer patient is a person with complex needs that requires multidisciplinary support not only for the cancer disease, but also for all related issues.

At the Candiolo Institute, patients who need or require it have access to specialists in different areas to receive nutritional support, physical therapy, pain therapy and management of other associated conditions.

The impact of cancer in a person’s life also affects the psychological sphere: falling ill with cancer is in fact always a traumatic event that affects all dimensions of the person and can generate anxiety, fear, anger, depression.

At the Candiolo Institute, alongside cutting-edge therapies, the treatment and care pathway always includes a qualified psycho-oncological support that helps the patient cope positively not only with treatment but also with the delicate phase of physical and psychological recovery.

It is also possible to participate in support groups psychological to compare with other people who have gone through or are going through the same experience.

The Social Service Department of the Candiolo Institute conducts information and orientation interviews to patients and their families on how to access services in the area and how to obtain welfare and social security benefits provided by law (disability, benefits for aids and prostheses, work leave, etc.).

The service operates on Wednesdays and Fridays from 9 a.m. to 1 p.m. (phone: 011 9933059).

With the conclusion of the course of treatment, the follow-up period begins during which, through a series of examinations and visits, the side effects of the therapies performed and their effectiveness are monitored and the patient’s functional recovery is assessed. Follow-up examinations are especially important to intercept any recurrences early so that appropriate therapy can be intervened. For the patient, they are also a valuable opportunity for dialogue with their medical specialist.

The follow-up course is planned with different timing and modalities depending on the type of lymphoma, the therapy performed and the response obtained, and the patient’s own characteristics.

Generally, checkups become less frequent as the years go by: in the first two years after the end of treatment they take place every three months, in the next three years every six months, and after the fifth year annually.

In addition to the physical examination and blood tests, follow-up checks usually include radiological examinations such as abdominal ultrasound, while CT and/or PET scans are requested if lymphoma recurrence is suspected.

Due to the high number of cases treated each year, the Candiolo Institute is a national reference for taking care of esophageal cancer. Our experience enables us to deal with even the most complex situations, always with a personalized approach built on the clinical and personal profile of each patient.

Establishing the treatment plan always starts with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that allow accurate assessment of the extent of the disease.

In addition, the Institute offers advanced and sophisticated laboratory investigations, including molecular and genomic analyses, which are critical for identifying biological features of cancer and guiding therapeutic decisions.

When indicated, surgery is performed with minimally invasive techniques (laparoscopic or thoracoscopic), which reduce operative trauma, promote faster recovery, and improve postoperative quality of life. Every treatment choice is defined within the GIC, ensuring a consistent and integrated approach.

As an IRCCS, the Candiolo Institute combines clinical practice with a strong vocation for scientific research. Patients can be evaluated for inclusion in active clinical trials, which provide a real opportunity to access innovative therapies not yet available in standard practice. Collaboration between care and research is a distinctive value that translates into concrete opportunities for the patient.

The Interdisciplinary Care Group takes care of the person at every stage: from diagnosis to treatment to follow-up, with attention to nutritional support, psychological health, and reintegration into daily life. The organization of checkups, visits and treatment is designed to ensure continuity and serenity, always valuing the human dimension of care.