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Case Studies

Real-world applications of RTpipeline in radiotherapy research

This section presents three detailed case studies demonstrating how RTpipeline addresses common challenges in radiotherapy data science. Each case study includes scientific background, step-by-step workflow, example code, and expected outcomes.

Overview

Case Study Domain Key Features Used
NTCP Modeling Dosimetric modeling DVH extraction, structure harmonization
Radiomics Signature Imaging biomarkers NTCV perturbations, robustness analysis
Distributed Reliability Aggregate radiomics validation Standardized local ETL, hash-bound packets

Case Study 1: NTCP Modeling for Late Rectal Toxicity

From Clinical DVHs to Robust NTCP Models: Single-Center Prostate RT with RTpipeline

Summary

This case study demonstrates how RTpipeline can be used to construct a normal tissue complication probability (NTCP) model for late rectal toxicity in a single-center retrospective prostate radiotherapy cohort. Starting from raw DICOM RTSTRUCT/RTPLAN/RTDOSE exports, RTpipeline standardizes structure nomenclature, computes a comprehensive set of dose-volume histogram (DVH) metrics for the rectum and bladder, and outputs an analysis-ready table that can be directly linked with clinical toxicity scores.

Scientific Background

Late rectal toxicity remains a clinically relevant adverse effect of definitive prostate radiotherapy, despite advances in planning and image guidance. Several dose-response relationships have been proposed (e.g., Quantitative Analyses of Normal Tissue Effects in the Clinic [QUANTEC] recommendations), but many are derived from relatively small cohorts or heterogeneous methodologies for DVH derivation and endpoint definition.

Research Question: Given a contemporary single-center cohort, what is the relationship between 3D planned rectal dose distributions and the risk of grade ≥2 late rectal toxicity, when DVH metrics are computed through a standardized, reproducible pipeline?

RTpipeline Workflow

graph TD
    A[DICOM Export from TPS] --> B[RTpipeline Ingestion]
    B --> C[Structure Harmonization]
    C --> D[DVH Computation]
    D --> E[Quality Control]
    E --> F[Data Export]
    F --> G[Clinical Linkage]
    G --> H[NTCP Modeling]

Step 1: Data Ingestion

Collect DICOM CT, RTSTRUCT, RTPLAN, and RTDOSE for all eligible prostate RT patients. Organize per-patient/per-course export directories.

Step 2: Structure Harmonization

Define a structure mapping where local variations are mapped to canonical labels:

# config.yaml - structure_mapping section
structure_mapping:
  RECTUM:
    patterns: ["Rectum", "RECT", "Rectum_full", "rectum*"]
  BLADDER:
    patterns: ["Bladder", "BLAD", "bladder*", "Vessie"]
  PTV_PROSTATE:
    patterns: ["PTV*prostate*", "PTV_7*", "PTV_SIB"]

Step 3: DVH Computation

Configure DVH metrics of interest:

dvh:
  metrics:
    - Dmean
    - Dmax
    - D2cc
    - V40Gy
    - V60Gy
    - V70Gy
    - V75Gy
  structures:
    - RECTUM
    - BLADDER
    - PTV_PROSTATE

Step 4: Quality Control

RTpipeline generates QC reports summarizing:

  • Missing structures
  • Extreme values (e.g., Rectum_V70Gy > 90%)
  • Dose grid characteristics
  • Frame-of-reference consistency

Step 5: Data Export and Clinical Linkage

Export produces a per-plan table with patient ID, plan ID, DVH metrics, and RT metadata.

Example Code

Running RTpipeline:

# Run pipeline on DICOM exports
docker run --rm -v /data:/data kstawiski/rtpipeline:latest \
  snakemake --cores 8 --configfile configs/prostate_ntcp.yaml

NTCP Modeling in Python:

import pandas as pd
from sklearn.model_selection import StratifiedKFold, cross_val_score
from sklearn.preprocessing import StandardScaler
from sklearn.linear_model import LogisticRegression
from sklearn.pipeline import Pipeline

# Load RTpipeline DVH output
dvh = pd.read_excel("_RESULTS/dvh_metrics.xlsx")

# Load clinical toxicity data
toxicity = pd.read_csv("clinical/toxicity.csv")
toxicity["late_rectal_tox_g2plus"] = (toxicity["grade"] >= 2).astype(int)

# Filter for rectum and merge
rectum = dvh[dvh['structure_name'] == 'RECTUM']
data = rectum.merge(
    toxicity[["patient_id", "late_rectal_tox_g2plus"]],
    on="patient_id"
)

# Define features
feature_cols = ["V40Gy", "V60Gy", "V70Gy", "Dmean_Gy", "Dmax_Gy"]
X = data[feature_cols]
y = data["late_rectal_tox_g2plus"]

# L2-regularized logistic regression
pipe = Pipeline([
    ("scaler", StandardScaler()),
    ("logreg", LogisticRegression(max_iter=500, solver="liblinear"))
])

cv = StratifiedKFold(n_splits=5, shuffle=True, random_state=42)
auc_scores = cross_val_score(pipe, X, y, cv=cv, scoring="roc_auc")
print(f"Cross-validated AUC: {auc_scores.mean():.3f} ± {auc_scores.std():.3f}")

Time-to-Event Analysis with Cox Regression:

from lifelines import CoxPHFitter

cox_df = data[feature_cols + ["followup_months", "late_rectal_tox_g2plus"]]

cph = CoxPHFitter()
cph.fit(
    cox_df,
    duration_col="followup_months",
    event_col="late_rectal_tox_g2plus"
)
cph.print_summary()

Expected Outcomes

  1. Reproducible DVH metrics computed with identical interpolation and volume definitions
  2. Transparent preprocessing fully documented in version-controlled configs
  3. Publication-ready data with clear provenance for Methods sections
  4. Shareable protocols enabling external validation at collaborating centers

Relevant Documentation

Case Study 2: Radiomics Signature for Treatment Response

Robust CT Radiomics for Response Prediction: IBSI-Aligned Feature Extraction with NTCV Perturbations

Summary

This case study demonstrates the use of RTpipeline for developing a radiomics signature to predict treatment response in thoracic radiotherapy. RTpipeline handles CT preprocessing, systematic field-of-view cropping around the target volume, PyRadiomics feature extraction using IBSI-defined feature families, and built-in robustness assessment with an adapted NTCV chain. The result is a feature set evaluated under the explicitly configured image and contour perturbations.

Scientific Background

Radiomics aims to quantify intratumoural heterogeneity and microenvironmental characteristics by extracting quantitative features from medical images. Numerous studies report associations between radiomic signatures and treatment response, but reproducibility is often limited by:

  • Inconsistent preprocessing
  • Non-standardized feature definitions
  • Unassessed feature robustness

Research Question: Can we identify a robust CT-based radiomics signature that predicts treatment response in lung cancer when features are extracted and stress-tested within a standardized, IBSI-informed framework?

The Robustness Problem

Without robustness assessment, radiomics models may rely on features that are:

  • Sensitive to small variations in image noise
  • Unstable under minor contour perturbations
  • Non-reproducible across different scanners

RTpipeline addresses this through an adapted NTCV perturbation chain (Noise, Translation, Contour, Volume) inspired by, but not identical to, Zwanenburg et al. (2019).

RTpipeline Workflow

graph TD
    A[CT + RTSTRUCT Export] --> B[Preprocessing]
    B --> C[FOV Cropping]
    C --> D[NTCV Perturbation Generation]
    D --> E[Radiomics Extraction × N perturbations]
    E --> F[ICC Computation per Feature]
    F --> G[Robust Feature Selection]
    G --> H[Model Training]

Step 1: Preprocessing Configuration

# Systematic preprocessing aligned with IBSI
preprocessing:
  resampling:
    spacing_mm: [1.0, 1.0, 3.0]
    interpolator: "sitkBSpline"
  intensity:
    normalize: true
    window_hu: [-1000, 400]

Step 2: CT Cropping

ct_cropping:
  enabled: true
  region: "thorax"
  superior_margin_cm: 2.0
  inferior_margin_cm: 2.0

Step 3: NTCV Perturbation Configuration

radiomics_robustness:
  enabled: true
  segmentation_perturbation:
    apply_to_structures: ["GTV*", "PTV*"]
    intensity: "standard"  # 135 states here because this example overrides V with 5 values

    # Volume perturbations (V)
    small_volume_changes: [-0.15, -0.10, 0.0, 0.10, 0.15]

    # Translation perturbations (T)
    max_translation_mm: 4.0

    # Contour randomization (C)
    n_random_contour_realizations: 2

    # Image noise (N)
    noise_levels: [0.0, 10.0, 20.0]  # HU std dev

Step 4: Robustness Thresholds

thresholds:
  icc:
    robust: 0.90      # Conservative: ICC ≥ 0.90
    acceptable: 0.75  # Standard: ICC ≥ 0.75
  cov:
    robust_pct: 10.0     # CoV ≤ 10%
    acceptable_pct: 20.0 # CoV ≤ 20%

Example Code

Running Radiomics with Robustness Assessment:

snakemake --cores 8 aggregate_radiomics_robustness

Feature Selection Based on Robustness:

import pandas as pd

# Load radiomics features and robustness metrics
features = pd.read_excel("_RESULTS/radiomics_ct.xlsx")
robustness = pd.read_excel(
    "_RESULTS/radiomics_robustness_summary.xlsx",
    sheet_name="robust_features"
)

# Select the exact ROI/source used by this model. A feature may be robust for
# one ROI/source and unstable for another.
robustness = robustness[
    (robustness["structure"] == "GTV_primary")
    & (robustness["segmentation_source"] == "Custom")
]
robust_feature_names = robustness["feature_name"].tolist()

# Filter the radiomics rows to the same exact ROI/source before selecting
# columns. `roi_original_name` avoids matching a cropped display suffix.
features = features[
    (features["roi_original_name"] == "GTV_primary")
    & (features["segmentation_source"] == "Custom")
].copy()
missing_features = sorted(set(robust_feature_names) - set(features.columns))
if missing_features:
    raise ValueError(f"Selected robustness features are absent: {missing_features}")
X_robust = features.loc[:, robust_feature_names]

print(f"Total features extracted: {len(features.columns)}")
print(f"Robust features retained: {len(X_robust.columns)}")
print(f"Retention rate: {100*len(X_robust.columns)/len(features.columns):.1f}%")

Building a Sparse Radiomics Signature:

from sklearn.linear_model import LogisticRegression
from sklearn.preprocessing import StandardScaler
from sklearn.model_selection import cross_val_score, StratifiedKFold
from sklearn.pipeline import Pipeline

# Load clinical response labels
clinical = pd.read_csv("clinical/response.csv")
data = features.merge(clinical[["patient_id", "response"]], on="patient_id")

X = data.loc[:, robust_feature_names]
y = data["response"]

# LASSO-regularized logistic regression for sparse signature
pipe = Pipeline([
    ("scaler", StandardScaler()),
    ("clf", LogisticRegression(
        penalty="l1",
        solver="saga",
        max_iter=2000,
        C=0.1
    ))
])

cv = StratifiedKFold(n_splits=5, shuffle=True, random_state=42)
auc = cross_val_score(pipe, X, y, cv=cv, scoring="roc_auc")
print(f"Robust features AUC: {auc.mean():.3f} ± {auc.std():.3f}")

# Identify selected features
pipe.fit(X, y)
coefs = pd.Series(pipe.named_steps["clf"].coef_[0], index=X.columns)
selected = coefs[coefs.abs() > 0.01].sort_values(key=abs, ascending=False)
print(f"\nSelected signature features:\n{selected}")

Visualizing Feature Robustness

import matplotlib.pyplot as plt

robustness_all = pd.read_excel(
    "_RESULTS/radiomics_robustness_summary.xlsx",
    sheet_name="global_summary"
)

fig, axes = plt.subplots(1, 2, figsize=(12, 4))

# ICC distribution
axes[0].hist(robustness_all["icc"], bins=30, edgecolor='black')
axes[0].axvline(0.90, color='green', linestyle='--', label='Robust (0.90)')
axes[0].axvline(0.75, color='orange', linestyle='--', label='Acceptable (0.75)')
axes[0].set_xlabel("ICC")
axes[0].set_ylabel("Number of Features")
axes[0].set_title("Feature Robustness Distribution")
axes[0].legend()

# ICC vs CoV scatter
axes[1].scatter(robustness_all["icc"], robustness_all["cov_pct"], alpha=0.5)
axes[1].axvline(0.90, color='green', linestyle='--')
axes[1].axhline(10, color='green', linestyle='--')
axes[1].set_xlabel("ICC")
axes[1].set_ylabel("Median within-subject CoV (%)")
axes[1].set_title("Robustness Quadrant Plot")

plt.tight_layout()
plt.savefig("robustness_analysis.png", dpi=150)

Expected Outcomes

  1. Curated feature set with quantified robustness under realistic perturbations
  2. Transparent feature and perturbation definitions suitable for peer review
  3. Sparse, interpretable signature for treatment response prediction
  4. Reproducible analysis with version-controlled configurations

Relevant Documentation

Case Study 3: Distributed Radiomics Reliability Analysis

One local method, one aggregate contract, multiple independently processed cohorts

Summary

Each participating site can run RTpipeline behind its own institutional boundary using a shared software version and analysis configuration. For radiomics reliability studies, a site exports only a hash-bound cohort-level summary packet. A coordinator validates every packet against the same contract and combines accepted aggregate rows.

This is distributed aggregate analysis. RTpipeline does not currently train or aggregate models across sites, provide secure aggregation, or implement differential privacy. A packet may still require institutional approval before transfer.

Workflow

flowchart LR
    C[Shared version, config, and contract] --> A1
    C --> A2
    C --> A3
    subgraph Site A
      D1[Local DICOM] --> A1[Local RTpipeline] --> P1[Validated aggregate packet]
    end
    subgraph Site B
      D2[Local DICOM] --> A2[Local RTpipeline] --> P2[Validated aggregate packet]
    end
    subgraph Site C
      D3[Local DICOM] --> A3[Local RTpipeline] --> P3[Validated aggregate packet]
    end
    P1 --> V[Coordinator validation]
    P2 --> V
    P3 --> V
    V --> R[Combined cohort-level table]

Raw DICOM and patient-level radiomic values are not fields in this packet contract. Literal cohort names are replaced by coded node labels, but those labels and cohort signatures are not an anonymity mechanism.

Step 1: Freeze the shared contract

CONTRACT_ID=consortium-ntcv-icc-v1
MINIMUM_SUBJECTS=5

rtpipeline federation contract \
  --contract-id "$CONTRACT_ID" \
  --minimum-subjects "$MINIMUM_SUBJECTS" \
  > contract.json

CONTRACT_SHA256=$(jq -r .contract_sha256 contract.json)

The digest covers the schema, semantic rules, permitted packet files, audit rules, and minimum cell size. All sites and the coordinator retain the same three values: contract ID, digest, and minimum-subject threshold.

Step 2: Process locally

Every site uses the same released RTpipeline version and reviewed configuration for DICOM organization, contours, radiomics preprocessing, perturbation chains, and cohort-level reliability summaries. Site-specific acquisition and anatomy can still affect the measurements; identical code does not make cohorts exchangeable.

Step 3: Export one aggregate packet per site

rtpipeline federation export \
  --input cohort_icc.parquet \
  --output packet-node-a13f \
  --node-id node-a13f \
  --contract-id "$CONTRACT_ID" \
  --contract-sha256 "$CONTRACT_SHA256" \
  --minimum-subjects "$MINIMUM_SUBJECTS"

The packet contains only manifest.json and deterministic metrics.csv.gz. Export fails if the table has an extra column, duplicate feature identity, invalid ICC interval, small cell, nonfinite value, path, URI, date, DICOM UID, hostname-like value, or direct identifier-like token.

Step 4: Validate and combine centrally

rtpipeline federation aggregate \
  --packet packet-node-a13f \
  --packet packet-node-b72c \
  --packet packet-node-c94d \
  --output aggregate \
  --contract-id "$CONTRACT_ID" \
  --contract-sha256 "$CONTRACT_SHA256" \
  --minimum-subjects "$MINIMUM_SUBJECTS"

The coordinator supplies its own contract values. It rejects a node that lowers the threshold, changes the schema, forges summary metadata, adds a file or symlink, or declares an audit result that cannot be reproduced. The aggregate manifest binds both files from every accepted packet by SHA-256.

What this design establishes

  1. Method identity: sites can run the same released code and configuration.
  2. Interface conformance: accepted packets have one exact row and metadata contract.
  3. Data minimization: the implemented packet schema has no raw DICOM, patient/course ID, patient-level feature, local path, date, or outcome field.
  4. Auditable aggregation: coordinator outputs retain packet hashes and node denominators.

It does not by itself establish cross-site biological transportability, clinical utility, site anonymity, legal permission to transfer aggregates, or federated learning performance. Those are separate scientific and governance questions.

Relevant documentation

Adapting Case Studies to Your Research

These case studies provide templates that can be adapted to your specific research context:

For Different Disease Sites

  • Head & Neck: Adjust structure mapping for parotids, larynx, constrictors
  • Breast: Include heart, LAD, lung substructures
  • CNS: Focus on brainstem, optic structures, hippocampi

For Different Endpoints

  • Overall Survival: Use time-to-event models (Cox regression)
  • Local Control: Binary classification or competing risks
  • Quality of Life: Ordinal regression or multi-endpoint modeling

For Different Modalities

  • MR-based Radiomics: Adjust preprocessing for MR intensity normalization
  • PET Radiomics: Configure SUV-based feature extraction
  • Multi-parametric: Combine CT + MR + PET features

Methods Boilerplate

The following text can be adapted for your Methods section:

DVH Extraction Methods

Dose-volume histogram metrics were extracted using RTpipeline (version 2.2.3) [cite]. Structure sets were harmonized to canonical nomenclature via a mapping dictionary. DVH curves were computed using [interpolation method] with a dose resolution of [X Gy]. The following metrics were derived: mean dose (Dmean), maximum dose (Dmax), dose to 2cc (D2cc), and volume receiving ≥[X Gy] (VXGy).

Radiomics Extraction Methods

Radiomic features were extracted using RTpipeline (version 2.2.3) [cite] with PyRadiomics 3.0.1 [cite] following Image Biomarker Standardisation Initiative (IBSI) feature definitions [cite]. Images were resampled to [X×X×X mm] voxels using [interpolation method]. Feature stability was assessed using an RTpipeline-adapted NTCV chain inspired by Zwanenburg et al. (2019) [cite], not an exact reimplementation. The configured [N] states per ROI combined Gaussian noise (σ = 0, 10, and 20 HU), superior-inferior translations (0 and +/-4 mm), two reproducible physical-space contour offsets, and distance-ranked volume adaptation to the closest voxel counts representing [LIST ACTUAL VOLUME TARGETS]. Every configured state was required to complete. CoV was computed within each patient/course/ROI/source and summarized by its cohort median. Structure/source/feature rows meeting ICC ≥ 0.90 and median within-subject CoV ≤ 10% were classified as robust.

References

  1. Zwanenburg A, et al. (2019). Assessing robustness of radiomic features by image perturbation. Scientific Reports 9:614. DOI: 10.1038/s41598-018-36938-4

  2. Zwanenburg A, et al. (2020). The Image Biomarker Standardization Initiative. Radiology 295(2):328-338. DOI: 10.1148/radiol.2020191145

  3. Koo TK, Li MY. (2016). A guideline of selecting and reporting ICC for reliability research. J Chiropr Med 15(2):155-163. DOI: 10.1016/j.jcm.2016.02.012

  4. Bentzen SM, et al. (2010). QUANTEC: Organ-specific papers. Int J Radiat Oncol Biol Phys 76(3):S1-S160.