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Hyperthermia and β-HCG Correlation Analysis

Analysis Date: November 25, 2025
Question: Is there any correlation between hyperthermia sessions and β-HCG tumor marker changes?
Status: ✅ Completed

Executive Summary

Based on comprehensive analysis of 49 hyperthermia sessions and 20 β-HCG tests spanning March-November 2025:

Finding: No significant statistical correlation between hyperthermia frequency and β-HCG changes (r=0.171, p=0.485).

Hyperthermia was consistently used as part of a multi-modal treatment approach alongside chemotherapy and immunotherapy, making it difficult to isolate its independent effect on tumor marker levels.

Data Overview

Treatment Timeline

  • Hyperthermia sessions: 49 total (May 9 - November 14, 2025)
  • Frequency: ~2-3 sessions per week
  • Context: Always used alongside chemotherapy/immunotherapy, not standalone
  • β-HCG tests: 20 measurements (March 21 - November 17, 2025)

Timeline Overlap

  • Hyperthermia period: May 9 - November 14, 2025
  • β-HCG tracking: March 21 - November 17, 2025
  • Overlap analysis period: May 9 - November 14, 2025 (16 β-HCG tests)

β-HCG Trajectory Analysis

Complete β-HCG Values Over Time

Date β-HCG Value Hyperthermia (7d) Hyperthermia (30d) Chemo (30d)
2025-03-21 70,482 0 0 0
2025-04-01 51,736 0 0 0
2025-04-29 220,096 0 0 2
2025-05-12 6,962 1 1 1
2025-06-04 4,968 3 7 1
2025-06-24 112,473 2 9 2
2025-07-02 240,422 2 9 3
2025-07-15 46,770 2 10 1
2025-07-21 95,787 2 8 2
2025-07-31 86,490 4 11 2
2025-08-07 7,324 0 8 2
2025-08-28 139 1 7 1
2025-09-05 82 2 8 1
2025-09-26 26 0 7 1
2025-10-03 20 3 8 1
2025-10-20 12 1 7 1
2025-10-29 9 1 7 1
2025-11-05 10 0 5 1
2025-11-14 24 0 3 0
2025-11-17 42 1 3 0

Key Milestones

  1. Initial Peak (Pre-Treatment): 70,482 (March 21)
  2. Post-Chemo Peak: 240,422 (July 2) - highest recorded value
  3. Major Drop: 240,422 → 46,770 in 13 days (July 2-15) with 4 hyperthermia sessions
  4. Breakthrough Drop: 7,324 → 139 in 21 days (Aug 7-28) with 6 hyperthermia sessions
  5. Lowest Point: 9 (October 29)
  6. Recent Uptick: 9 → 42 (Oct 29 - Nov 17) despite continued hyperthermia

Interval-by-Interval Analysis

β-HCG Changes Between Tests

Period Days β-HCG Change % Change Hyperthermia Sessions
Mar 21 → Apr 1 11 -18,746 -26.6% 0
Apr 1 → Apr 29 28 +168,360 +325.4% 0
Apr 29 → May 12 13 -213,134 -96.8% 1
May 12 → Jun 4 23 -1,994 -28.6% 7
Jun 4 → Jun 24 20 +107,505 +2,163.9% 5
Jun 24 → Jul 2 8 +127,949 +113.8% 3
Jul 2 → Jul 15 13 -193,652 -80.5% 4
Jul 15 → Jul 21 6 +49,017 +104.8% 1
Jul 21 → Jul 31 10 -9,297 -9.7% 5
Jul 31 → Aug 7 7 -79,166 -91.5% 0
Aug 7 → Aug 28 21 -7,185 -98.1% 6
Aug 28 → Sep 5 8 -57 -41.0% 3
Sep 5 → Sep 26 21 -56 -68.3% 5
Sep 26 → Oct 3 7 -6 -23.1% 2
Oct 3 → Oct 20 17 -8 -40.0% 4
Oct 20 → Oct 29 9 -3 -25.0% 1
Oct 29 → Nov 5 7 +1 +11.1% 1
Nov 5 → Nov 14 9 +14 +140.0% 1
Nov 14 → Nov 17 3 +18 +75.0% 0

Statistical Analysis

Correlation Testing

Pearson Correlation Analysis: - Coefficient (r): 0.171 - P-value: 0.485 - Interpretation: No significant correlation - Confidence: Not statistically significant (p > 0.05)

Pattern Observations

During β-HCG Declines (12 periods): - Average hyperthermia sessions: 3.2 sessions - Average decline: -57.4%

During β-HCG Increases (7 periods): - Average hyperthermia sessions: 1.6 sessions - Average increase: +446.1%

Important Note: This inverse pattern (more hyperthermia during declines) could indicate: 1. Hyperthermia was intensified when treatment was showing positive response 2. Scheduling coincidence with chemotherapy cycles 3. Not causation, as confounding factors (chemo timing, dose) not controlled

Treatment Context & Confounding Factors

Multi-Modal Treatment Approach

Chemotherapy Cycles: 1. April 22: Chemo #1 (60% Paclitaxel, 60% Carboplatin) 2. May 14: Chemo #2 (50% Paclitaxel, 75% Carboplatin) 3. June 4: Immunotherapy #2 only (Pembrolizumab) 4. June 25: Chemo #3 + Immuno #3 5. July 16: Chemo #4 + Immuno #4 6. July 21-26: VIP #1 protocol (5-day intensive) 7. Aug 11-16: VIP #2 protocol 8. Sep 8-13: VIP #3 protocol 9. Oct 6-11: VIP #4 protocol (70% dose)

Hyperthermia Integration: - Started May 9, 2025 (after initial chemo response) - Consistently 2-3 sessions per week - Always concurrent with chemotherapy/immunotherapy - Never used as standalone treatment

Why Correlation is Difficult to Establish

  1. Simultaneous Treatments: Hyperthermia always combined with chemotherapy
  2. Chemo Dose Variations: Doses ranged from 50-100% across cycles
  3. Protocol Changes: Switch to VIP protocol in July (major β-HCG drops followed)
  4. Disease Biology: Natural tumor marker fluctuations
  5. Timing Confounds: More hyperthermia scheduled when showing positive response

Key Observations

1. Hyperthermia Started After Initial Decline

  • β-HCG was already dropping before hyperthermia began (May 9)
  • First major drop: 220,096 → 6,962 (Apr 29 - May 12) with only 1 hyperthermia session

2. Most Dramatic Drops Associated with VIP Protocol

  • Aug 7 → Aug 28: 7,324 → 139 (-98.1%) - post VIP #2
  • Jul 2 → Jul 15: 240,422 → 46,770 (-80.5%) - during VIP #1
  • Jul 31 → Aug 7: 86,490 → 7,324 (-91.5%) - post VIP #1

3. Recent Uptick Despite Continued Hyperthermia

  • Oct 29 - Nov 17: β-HCG rose from 9 → 42
  • Hyperthermia continued at 1-3 sessions per period
  • No chemotherapy in November (last was Oct 6-11)
  • Concern: Suggests other factors driving tumor marker changes

4. Hyperthermia Frequency Relatively Consistent

  • Averaged 2-3 sessions per week throughout treatment
  • No clear pattern of increased sessions = decreased β-HCG
  • Both major declines and increases occurred with similar hyperthermia frequency

Clinical Interpretation

What the Data Suggests

Hyperthermia Role: - Integrated component of multi-modal treatment strategy - Cannot isolate independent effect on β-HCG - May support overall treatment but not primary driver of tumor marker changes

Primary β-HCG Drivers (Based on Data): 1. Chemotherapy regimen (especially VIP protocol) 2. Chemotherapy dose intensity 3. Treatment combinations (chemo + immunotherapy) 4. Disease biology/tumor heterogeneity

Concerning Trend

Recent β-HCG Rise (Oct 29 - Nov 17): - 9 → 42 (367% increase over 19 days) - Occurred during continued hyperthermia - No active chemotherapy in November - Implications: - Possible treatment resistance or disease progression - May need treatment adjustment/intensification - PET scan (Nov 17) crucial for anatomical correlation

Recommendations

For Medical Team Discussion

  1. Recent β-HCG Uptick:
  2. Review PET scan results (Nov 17, 2025)
  3. Assess need for treatment intensification

  4. Consider biopsy if viable tumor identified

  5. Treatment Strategy:

  6. Evaluate efficacy of current hyperthermia protocol
  7. Discuss role within overall treatment plan

  8. Consider cost-benefit given statistical findings

  9. Monitoring:

  10. Continue close β-HCG monitoring (weekly/bi-weekly)
  11. Correlate tumor markers with imaging
  12. Track response to any treatment modifications

For Data Tracking

  1. Enhanced Documentation:
  2. Record hyperthermia parameters (temperature, duration)
  3. Note any variations in protocol

  4. Track subjective response/side effects

  5. Future Analysis:

  6. Longer time series once treatment stabilizes
  7. Consider time-lagged correlations (effect after X days)
  8. Compare periods with/without hyperthermia if treatment adjusted

Limitations of This Analysis

  1. Small Sample Size: 19 intervals between 20 tests
  2. Confounding Variables: Cannot isolate hyperthermia effect from chemotherapy
  3. No Control Group: No periods without hyperthermia during treatment
  4. Timing Variability: Irregular intervals between blood tests (3-28 days)
  5. Missing Data: Hyperthermia session parameters (temperature, duration) not analyzed
  6. Recent Data: Uptick trend is very recent, need longer follow-up

Conclusion

Based on comprehensive analysis of your complete treatment data:

No statistically significant correlation exists between hyperthermia frequency and β-HCG changes (r=0.171, p=0.485).

Hyperthermia has been consistently integrated into your multi-modal treatment approach, but the data suggests: - Primary β-HCG drivers: Chemotherapy regimen and dose intensity - Hyperthermia role: Supportive component, independent effect unclear - Recent concern: β-HCG rising despite continued hyperthermia and regular sessions

Most Important: The recent β-HCG uptick (9 → 42) warrants urgent discussion with your oncologist, as it suggests factors beyond hyperthermia frequency are influencing tumor marker levels.

Data Sources

  • Treatment Timeline: data/processed/treatment_timeline.json
  • Blood Tests: data/processed/blood_tests.csv
  • Analysis Period: March 21 - November 17, 2025
  • Hyperthermia Sessions: 49 documented sessions
  • β-HCG Tests: 20 measurements
  • Statistical Analysis: Python (scipy.stats, pandas)

Analysis completed: November 25, 2025
Next review: After treatment adjustments or with additional 4-6 weeks of data