CNA511- gestational trophoblastic neoplasia

Hi everyone, my name's Ashley and I work on a gynaecology oncology ward. Today I'm talking to you about a patient with gestational trophoblastic neoplasia. The patient Julia was a 39 year old female diagnosed with FIGO stage 1, whose score 4, low risk gestational trophoblastic neoplasia or GTN for short. Her diagnosis followed the surgical evacuation of a partial molar pregnancy. So just in background and clinical context, a partial molar pregnancy results from an ovum being fertilised by two sperm, leading to an excess of paternal DNA. This results in abnormal placental development, which unfortunately means that the pregnancy is non-viable and requires surgical removal. Gestational trophoblastic neoplasia refers to a spectrum of rare malignant trophoblastic tumours arising from placental tissue.

In Julia's case, residual trophoblastic tissue persisted and invaded the myometrium, which is a condition known as an invasive mole, which is a sub-type of GTM. GTN is typically characterised by persistently elevated serum beta HCG levels. Julia underwent a comprehensive diagnostic workup including blood tests and imaging, which showed an enlarged uterus but no discrete mass. Chest X-ray and CT brain came back NAD and all other blood tests were within normal limits apart from the elevated beta HCD. Medically, um, Julia had no significant uh medical conditions and socially she resided with her husband and two year old son. She was employed as an office worker, and she had limited local support because her family resided interstate, but she did report feeling well supported by close friends. Julia's treatment followed current clinical guidelines from EviQ consisting of a single agent chemotherapy with methotrexate. She received 50 milligrams of methotrexate intramuscularly on days 135, and 7, along with 150 milligrams of calcium folinate orally on days 246, and 8, and each treatment cycle lasted 14 days. Methotrexate is an anti-metabolite chemotherapy chemotherapeutic agent.

It exerts its cytotoxic effect by inhibiting the enzyme DHFR, thereby preventing the formation of tetrahydrofolic acid, which is a crucial cofactor in DNA synthesis and cellular replication. This inhibition particularly affects rapidly dividing cells such as trophoblastic cells, making methotrexate an effective treatment for gestational trophoblastic neoplasia. Methotrexate is commonly used as a first line therapy for patients with low risk GTN due to its relatively mild toxicity profile and limited side effects. This was especially important for Julia, who was balancing full-time employment and parenting responsibilities with minimal family support. Studies have demonstrated that low risk GTN responds well to methotrexate regardless of the administration route with an 88 complete response rate in patients. As an outpatient, Julia received methotrexate via the IM route, according to EviQ protocols, allowing her to fit her treatment into her work schedule, typically during her lunch break, thereby minimising disruption to her daily routine.

Methotrexate has significantly improved survival in GTN reducing the need for surgical intervention, which, which carries risks such as uterine perforation and haemorrhage due to the vascular nature of trophoblastic tissue. Calcium folinate, known as folinic acid, is administered alongside methotrexate to mitigate its toxic effects on healthy cells. While methotrexate inhibits nucleic acid synthesis by blocking folic acid activation, calcium folinate provides an active form of folic acid, enabling normal DNA synthesis to continue despite methotrexate's action. Administering calcium folinate approximately 24 hours after methotrexate significantly reduces the side effects such as uh hepatotoxicity, GI disturbances, and oral mucositis.

This protective role is a critical component of methotrexate-based regimens, especially in outpatient settings where minimising adverse effects is essential for maintaining quality of life and adherence to treatment. GTN produces elevated levels of beta HCG, making it a reliable biomarker for disease monitoring, treatment response and surveillance. Julia underwent fortnightly beta HCG testing alongside routine FBC UEC and LFTs to monitor for methotrexate-related toxicity. Given methotrexates distribution in the liver, kidneys and GI tract, and it's predominantly renal excretion, monitoring renal function, particularly particularly EGFR is essential. Following normalisation of Julius beta HCG levels, methotrexate therapy was continued for 3 additional consolidation cycles before treatment was ceased. Evidence suggests that patients receiving only 2 consolidation cycles have a higher risk of relapse compared to those who receive 3. Resistance to methotrexate, which is indicated by rising beta HCG levels during treatment, may necessitate escalation to second line therapy such as ainomycin D or combination regimens like Emmaco. Thankfully in Julia's case, she responded well to methotrexate, and she required 9 cycles in total before she was discharged.

Research indicates that patients diagnosed with GTN often require additional psychosocial support during hospitalisation and after discharge. Julia was advised to avoid pregnancy for at least 12 months following the completion of her treatment. This recommendation is based on evidence that the first year post-treatment carries the highest risk of disease reoccurrence. Moreover, elevated beta HCG levels associated with early pregnancy could potentially obscure early signs of relapse, thereby delay delaying timely diagnosis and treatment. Julia experienced ongoing anxiety about the possibility of future molar pregnancies, reoccurrence of GTN with subsequent pregnancies, and concerns regarding her fertility. While studies suggest that single agent chemotherapy does not negatively impact fertility or pregnancy outcomes, a significant 88% of GTN patients report moderate to severe intrusive thoughts and avoidant behaviours. Additional research shows elevated levels of emotional stress among GTN patients, with one study finding that 27% of patients experience symptoms of depression shortly after diagnosis. The abruptness of the diagnosis also results in women feeling sad, uncertain and powerless.

These psychological effects tend to be more pronounced in patients who already have children or have experienced previous pregnancy loss. Thankfully in Australia, organisations such as Cancer Council and Fair Work Ombudsman advocate for flexible work arrangements for cancer patients and their caregivers. This may, um, these may include remote work, modified hours or adjusted duties. Julia was promptly referred to the hospital's clinical psychology team, where she began attending weekly sessions to help her cope emotionally. Studies highlight the crucial role of multidisciplinary teams in recognising signs of depression and supporting patients through the emotional impact of treatment. Research also indicates that receiving psychological support soon after pregnancy loss can have lasting benefits for mental health. Clinical guidelines from the psycho-oncology cooperative Research Group, Recommend early detection and treatment of anxiety and depression, as this can lead to improved treatment compliance, better communication between patients and doctors, and fewer clinic visits. With timely screening, evaluation and management, Julia was able to make good use of these psychological services, which greatly reduced her emotional distress during treatment.

After being discharged, she was encouraged to continue her psychological care either privately or through cancer support groups such as Counterpart or Rare Cancers Australia. This recommendation aligns with research showing that women with GTN often prefer to lean on their social networks and peer support. Joining support groups has also been shown to ease anxiety and depression in people with various types of cancer, and group therapy is also known to be effective in improving mental health across different cancer diagnoses. Upon reflection, the multidisciplinary team collab collaborated effectively to provide Julia with evidence-based and supportive care throughout her treatment. She received comprehensive written written information about her condition.

This is important because research suggests that many women diagnosed with GTN report insufficient access to clear and comprehensive information, which can contribute to confusion, anxiety and emotional distress. Secondly, there was considerable attention given to Julia's mental health early on in the treatment process, including referrals to clinical psychology services and peer support groups. Thirdly, the hospital's GTN service is managed by a dedicated but small team comprising of 1 medical doctor and 3 GTN specialist nurses. This structure is particularly significant given that Cancer Australia's clinical guidelines recommend designating a single healthcare professional within the treatment team to oversee assessment, referral and follow-up. This approach has been shown to reduce patient anxiety and depression by improving care, continuity and coordination. Unfortunately, routine screening for anxiety and depression remains inconsistent across many healthcare settings with wide variability in how patients are referred, treated and followed up.

Therefore, I believe it is essential to implement formalised psychological screening at the point of GTN diagnosis. Tools such as the distress thermometer and the hospital anxiety and depression scale, both recommended by Cancer Australia, should be routinely used to identify patients in need of mental health support. In addition to streamlining screening practises, I also believe there is a need to improve the delivery of care within the GTN service itself. At present, treatments are delivered on a busy gynaecology oncology ward by multiple nurses, many of whom are unfamiliar with the patients. This often results in long wait times depending on staff availability and limits continuity of care. A more consistent and streamlined service would enhance the patient experience and ensure more timely and coordinated care. I do have some questions for discussion. Um, number one, have you ever heard of GTN before or cared for GTN patients? If so, how is low risk GTN treated at your health facility? If not, what was the most surprising or interesting thing you learned about GTN today? Do you use methotrexate in your health facility? If so, what types of condition is it used for? And what are some ways that your health facility ensures that patients affected by cancer are psychosocially supported? Uh, these are my references, and I thank you for listening.