Health And Me Desk

Stage IV Melanoma: When a Difficult Cancer Shows an Unexpected Response

<a href="https://www.healthandme.com/health/melanoma">Melanoma</a> is often considered one of the more challenging cancers to treat, particularly when it has spread to distant organs. For early-stage disease, surgery remains an important treatment option. But once melanoma reaches stage IV, treatment becomes considerably more complex.

Understanding The Biology Of Advanced Melanoma

According to Dr. Mandeep Singh Malhotra, Cheif Mentor AOHC, cytotoxic chemotherapy has traditionally had a limited role in <a href="https://www.healthandme.com/health-news/sunscreen-is-a-health-essential-uk-skin-cancer-survivor-urges-govt-to-scrap-tax-article-155981799" data-type="tilCustomLink">melanoma</a>, while immunotherapy has changed the treatment landscape for many patients.

When melanoma is detected at an early stage and can be completely removed, surgery is generally considered the preferred treatment. Depending on the disease, this can involve removal of the primary tumour and assessment or treatment of regional lymph nodes.

But stage IV <a href="https://www.healthandme.com/health/melanoma">melanoma</a> presents a very different challenge.

A Complex Case With Multiple Tumour Sites

Dr. Malhotra recalls the case of Sarah, who came to the team with multiple nodules in the scapular region. There were also lesions on both legs and a lesion in the pancreas. So there were multiple nodules. One in the right side of the leg, another in the left side of the leg. And there was a lesion in the pancreas.

Rather than relying on a standard treatment approach alone, the team first tried to understand the biology of the disease. As a standard protocol for this type of case, we first try to understand the disease biology. In Sarah’s case, the team used extensive testing, including chemosensitivity testing, transcriptomic analysis and next-generation sequencing.

Also read: <a href="https://www.healthandme.com/health-wellness/cancer-should-be-made-notifiable-in-india-say-experts-heres-why-article-156001042" data-type="tilCustomLink">Cancer Should Be Made Notifiable In India, Say Experts: Here’s Why</a>

When Imaging Initially Suggests Progression

The results suggested sensitivity to certain drugs. When we analysed those reports, we were able to understand that cytotoxic drugs like temozolomide were effective. And checkpoint inhibitors like <a href="https://www.healthandme.com/health-news/moderna-mercks-personalized-mrna-vaccine-ushering-in-a-new-era-in-cancer-care-article-155950710" data-type="tilCustomLink">pembrolizumab</a>, nivolumab were effective.

Based on these findings, the team developed a treatment protocol in which the main component was an immune checkpoint inhibitor along with low-dose temozolomide. Other agents, including lower doses of anti-VEGF, anti-FGF and CDK inhibitors, were also incorporated based on the analysis.

After around four weeks, the response became difficult to interpret on imaging. The PET scan suggested that all the lesions have had a pseudo progression.

Pseudo progression is a recognised phenomenon during immunotherapy. A tumour may appear larger initially because of immune-cell infiltration, even when the treatment is actually producing an anti-tumour response. 

This is particularly relevant in melanoma treated with immune checkpoint inhibitors. However, doctors cannot simply assume that every apparent progression is pseudo-progression; true progression must also be considered and confirmed through Histopathology

Also read: <a href="https://www.healthandme.com/health-news/french-court-links-flight-attendants-breast-cancer-to-workplace-radiation-how-does-flying-increase-cancer-risk-article-155995063" data-type="tilCustomLink">French Court Links Flight Attendant’s Breast Cancer To Workplace Radiation; How Does Flying Increase Cancer Risk?</a>

Histopathology Reveals A Dramatic Treatment Response

The team then proceeded with surgery, removing the nodules from the scapular region and both thighs. The specimens were sent for histopathological examination. And histopathology results were amazing. The <a href="https://www.healthandme.com/nutrition/for-the-first-time-study-links-one-sugary-drink-a-day-to-higher-stomach-cancer-risk-article-155800750" data-type="tilCustomLink">tumours</a> had gone necrotic.

The pathology showed extensive treatment-related changes, with inflammation and fibrosis around the nodules and only small areas containing viable melanoma cells.

Also read: <a href="https://www.healthandme.com/health-news/daraxonrasib-us-fda-approves-once-daily-pill-for-metastatic-pancreatic-cancer-article-155991835" data-type="tilCustomLink">Daraxonrasib: US FDA Approves Once-Daily Pill for Metastatic Pancreatic Cancer</a>

What Comes Next For The Patient?

For now, the plan is to continue the treatment for a few more cycles and then reassess the pancreatic lesion. The team is considering NanoKnife (irreversible electroporation) for the pancreatic lesion followed by Vaccines. 

Certain <a href="https://www.healthandme.com/health/cancer">cancer</a> vaccines are being developed in certain labs in Germany and Europe and they are available for our patients in India on compassionate grounds. It's a very, very good response. And to achieve disease NED in <a href="https://www.healthandme.com/health-news/does-sunscreen-really-raise-skin-cancer-risk-what-the-470000-person-study-found-article-155692159" data-type="tilCustomLink">stage four melanoma</a>, I think we are really lucky and it's all due to the grace of God.

Why Individualised Treatment Matters In Stage IV Disease

Healthy and Hearty Picks: Cancer Cases Rising in India | Causes, New Treatments & Prevention

The case also highlights an important point about advanced melanoma: treatment may need to be individualised according to the biology of the disease and the patient's response. At the same time, he stresses the need for hope. I hope that more people can benefit from this protocol and use this protocol to treat melanomas across the world.

For Sarah, the journey is still ongoing. The next step will be to reassess the pancreatic lesion and determine whether further local treatment can help achieve no evidence of disease (NED). A stage IV melanoma involving multiple sites, including the pancreas, reaching a point where NED may become a possibility is certainly an encouraging development. But it remains an individual clinical experience, rather than proof that the same protocol will work for every patient with metastatic melanoma.

By Dr. Mandeep Singh Malhotra, Director of Surgical Oncology at CK Birla Hospital and Chief Mentor at AOHC

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Melanoma is often considered one of the more challenging cancers to treat, particularly when it has spread to distant organs. For early-stage disease, surgery remains an important treatment option. But once melanoma reaches stage IV, treatment becomes considerably more complex.Understanding The Biology Of Advanced MelanomaAccording to Dr. Mandeep Singh Malhotra, Cheif Mentor AOHC, cytotoxic chemotherapy has traditionally had a limited role in melanoma, while immunotherapy has changed the treatment landscape for many patients. When melanoma is detected at an early stage and can be completely removed, surgery is generally considered the preferred treatment. Depending on the disease, this can involve removal of the primary tumour and assessment or treatment of regional lymph nodes.But stage IV melanoma presents a very different challenge.A Complex Case With Multiple Tumour SitesDr. Malhotra recalls the case of Sarah, who came to the team with multiple nodules in the scapular region. There were also lesions on both legs and a lesion in the pancreas. So there were multiple nodules. One in the right side of the leg, another in the left side of the leg. And there was a lesion in the pancreas.Rather than relying on a standard treatment approach alone, the team first tried to understand the biology of the disease. As a standard protocol for this type of case, we first try to understand the disease biology. In Sarah’s case, the team used extensive testing, including chemosensitivity testing, transcriptomic analysis and next-generation sequencing.Also read: Cancer Should Be Made Notifiable In India, Say Experts: Here’s WhyWhen Imaging Initially Suggests ProgressionThe results suggested sensitivity to certain drugs. When we analysed those reports, we were able to understand that cytotoxic drugs like temozolomide were effective. And checkpoint inhibitors like pembrolizumab, nivolumab were effective. Based on these findings, the team developed a treatment protocol in which the main component was an immune checkpoint inhibitor along with low-dose temozolomide. Other agents, including lower doses of anti-VEGF, anti-FGF and CDK inhibitors, were also incorporated based on the analysis.After around four weeks, the response became difficult to interpret on imaging. The PET scan suggested that all the lesions have had a pseudo progression.Pseudo progression is a recognised phenomenon during immunotherapy. A tumour may appear larger initially because of immune-cell infiltration, even when the treatment is actually producing an anti-tumour response. This is particularly relevant in melanoma treated with immune checkpoint inhibitors. However, doctors cannot simply assume that every apparent progression is pseudo-progression; true progression must also be considered and confirmed through HistopathologyAlso read: French Court Links Flight Attendant’s Breast Cancer To Workplace Radiation; How Does Flying Increase Cancer Risk?Histopathology Reveals A Dramatic Treatment ResponseThe team then proceeded with surgery, removing the nodules from the scapular region and both thighs. The specimens were sent for histopathological examination. And histopathology results were amazing. The tumours had gone necrotic. The pathology showed extensive treatment-related changes, with inflammation and fibrosis around the nodules and only small areas containing viable melanoma cells.Also read: Daraxonrasib: US FDA Approves Once-Daily Pill for Metastatic Pancreatic CancerWhat Comes Next For The Patient?For now, the plan is to continue the treatment for a few more cycles and then reassess the pancreatic lesion. The team is considering NanoKnife (irreversible electroporation) for the pancreatic lesion followed by Vaccines. Certain cancer vaccines are being developed in certain labs in Germany and Europe and they are available for our patients in India on compassionate grounds. It's a very, very good response. And to achieve disease NED in stage four melanoma, I think we are really lucky and it's all due to the grace of God.Why Individualised Treatment Matters In Stage IV Disease      The case also highlights an important point about advanced melanoma: treatment may need to be individualised according to the biology of the disease and the patient's response. At the same time, he stresses the need for hope. I hope that more people can benefit from this protocol and use this protocol to treat melanomas across the world.For Sarah, the journey is still ongoing. The next step will be to reassess the pancreatic lesion and determine whether further local treatment can help achieve no evidence of disease (NED). A stage IV melanoma involving multiple sites, including the pancreas, reaching a point where NED may become a possibility is certainly an encouraging development. But it remains an individual clinical experience, rather than proof that the same protocol will work for every patient with metastatic melanoma.By Dr. Mandeep Singh Malhotra, Director of Surgical Oncology at CK Birla Hospital and Chief Mentor at AOHC

stage iv melanoma: when a difficult cancer shows an unexpected response

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